Section A: Cellular Physiology

General Instructional Objectives - An understanding of basic cellular physiology

A. To describe the cell membrane and its properties

G. To describe the composition of intracellular fluid and its regulation including the role of the
sodium-potassium pump
Distribution of ions across cell membrane

Cell membrane 2 – semipermeable phospholipid bilayer, with polar heads on the outside & lipophilic tails on the
inside.
Integral proteins - traverse the whole membrane,
glycoproteins attached carbohydrate moiety
Peripheral proteins - sit on the cytoplasmic or
extracellular surface.

Functions
1. Maintain resting membrane potential
2. Controlling cell permiability
3. Transportation of particles – ion
pumps/channels & carrier proteins
4. Anchoring of the cytoskeleton to
maintain cell shape
5. Attaching to the extracellular matrix to
help group cells together to form tissues
6. Receptors to allow chemical messages to pass between cells and systems
7. Enzymes – participate in cellular metabolism & immunity

Resting membrane potential

Cell membranes have electrical charge across them with the inside 70-80mV negative with respect to the outside. The
electrical potential depends on…
1. The selective membrane permeability to ions – more important & can change
2. The distribution of ions across the membrane

The RMP is due to the equilibrium of electrochemical gradients affecting K + ions - Membranes are
semipermeable to ions - K+ moves across easily, but most others do not. K+ permeability at rest is greater than Na+.
1. The concentration gradient for K+ faciliatates its movement out of the cell: 150mM inside and 5mM
outside.
2. This is opposed by an electrical gradient. As the membrane is impermeable to other cations the movement
of positively charged K+ produces a negative charge on the inside of the cell. This charge opposes further
movement of K+ out of the cell.
At the RMP of  -70mV the chemical & electrical gradients acting on K+ ions balance.
Only a small number of K+ ions have to move to produce the RMP. At -70mV the difference between number of +ve
& -ve charges is only 0.000002%

Anions – proteins are the main intracellular anions, but they are impermeable & have little effect on RMP. The
primary extracellular anion is Cl-, which is permeable, but sets up a similar potential to K+.
Cations – other cations contribute little to RMP as the membrane is impermeable to them. If the membrane was
permeable to Na+ then the potential would be completely reversed.

Function of the membrane potential

Allows electrical communication between cells. E.g. nerve cells transmit messages, cardiac cells  autorhythmicity &
skeletal muscles cells  contraction by a progressive propagated reversal of the membrane potential.

Sodium – at RMP -70mV both the electrical & chemical gradients tend to push sodium into the cell, despite its
relative impermeability. If the Na+ that does get in were not actively removed then the membrane potential would
gradually diminish.
Na+:K+ATPase pumps – is a transmembrane protein pump with a large  subunit (ATPase activity) & a smaller 
subunit. 2 K+ ions enter for 3 Na+ ions extruded. Hence it is electrogenic & contributes to the negative RMP as it
extrudes more +ve ions than it admits.

Calcium
Used as a physiological trigger. Intracellular concentrations are kept low  0.1M. Extracellular  5mM. The chemical
& electrical gradient also pushes Ca2+ inwards. Increased membrane permeability to Ca2+ depolarises cells. 2
mechanisms remove Ca2+ from cells…
1. Membrane bound pump – low intracellular Ca2+ concentrations, activated by calmodulin, energy requiring
– 1ATP per Ca2+ ion extruded.
2. Exchange of internal Ca2+ for external Na+ - high intracellular Ca2+ concentrations, driven by Na + moving
down its concentration gradient.

01B5 97A1 Describe the structure and function of voltage gated ion channels.  

Voltage gated ion channels – Na+, K+ or Ca2+ channels that are ‘gated’ by the membrane voltage.
General structure - transmembrane protein with a central pore whose opening & closing is due to change in
configuration of the proteins. Can be ion specific or general. Ions move down there electrochemical gradient.
General Function – dependence on voltage change for configurational changes  alteration of ion conductance,
possibility of channel activation & inactivation

Voltage clamp – positive feedback between depolarisation & Na+ permeability can be eliminated by passing current
through a membrane. The current required to maintain a constant membrane potential reflects the ionic flow through
the channels.
Patch clamp – a small area of membrane is voltage-clamped so that individual channels can be observed.

Sodium channels
Structure: transmembrane protein made up of 4 domains each with 6 alpha
helices (S1-S6). S1-S3 are –ve charged & line a pore through the membrane.
In the resting state a +ve charged sensor is attracted by the –ve pore.
Opening: depolaristation to threshold potential swings the sensor towards the
outside of the membrane & the activation gate opens. The +ve charged S4
segment moves outwards, the whole structure undergoes a conformational
change, & the central pore opens for for  0.7msec.
Density: 500-1000 per m2
Ionic permeability: Li+ 1.1, Na+ 1, K+ 1/12, rubidium 1/40
Block: Tetrodotoxin & saxitoxin block the mouth of the channel from outside.
LA block the channel after diffusing through the membrane. Function can be
reduced by [H+]. Quaternary ammonium ions block, but only from the
inside.
Inactivation: by a particle which can be removed by the internal application of
the enzyme pronase. Sea anemones & scorpions produce peptide toxins that can
prevent inactivation  hyperexcitation & pain.
Function: Nerve action potentials
Potassium channels
Types: several identified, but delayed rectifier potassium channels are involved in nerve APs
Structure: 3-3.3 diameter
Density: 36 per m2
Ionic permeability: K+, thallium, rubidium & ammonium. Despite being smaller Na + ions cannot pass as they cross
with a hydration shell which is too big for delayed rectifier channels.
Block: caesium, barium, strychnine & quinidine. Quaternary ammonium ions block, but only from the inside.
Inactivation: No inactivating mechanism.

Calcium channels
Types: T (transient), N (inactivated at very –ve potentials, neuronal) & L (long lasting) types which differ in
sensitivity to blockes & threshold potentials.
Structure: Molecular sequence very similar to Na channels
Ionic permeability: Ca2+
Block: Divalent cations (manganes, nickel, cobalt + cadmium), verapamil, dihydropyridines & cone shell toxin
Function: ventricular muscle, nerve terminals

Transient Neuronal Long Lasting

Threshold potential (mV) -70 -10 -10
Cadmium block + +++ +++
Cone toxin block + +++ +++
Dihydropyridine block - - +++

93A2 What are 'membrane channels'? How are they investigated? Describe one commonly -
interfered with in Anaesthesia

B. To describe the functions of mitochondria, endoplasmic reticulum, and other organelles

Lysosomes – irregular acid containing structures that digest endocytosed bacteria & defunct cell components.

Peroxisomes – contain enzymes which catalyse a variety of anabolic & catabolic reactions.

Cytoskeleton – a system of fibers (microtubules, intermediate filaments/microfilaments & adhesion complexes) that
maintain the structure of the cell, allow the cell to change shape & move and allow organelles to move within the cell.

Centrisomes – consists of 2 centrioles. They duplicate & monitor the steps in cell division.
Cilia – Cell projections used to propel mucus & other substances over the surface of epithelia.

Cell adhesion molecules – anchor cells to each other & the basal lamina.

Nucleus – surrounded by a nuclear envelope (membrane) & contains the cellular blueprint (chromosomes, made of
DNA) and a nucleolus where ribosomes are produced.

Ribosomes – the sites of protein synthesis. Contain a large & small subunit. Are found on the rough ER or free in the
cell.

Golgi apparatus – involved in processing proteins formed by ribodomes.

98B7 Briefly describe structure of mitochondria. Outline the metabolic processes that occur in 64%
mitochondria

Mitochodria – membrane enclosed organelles found in most eukaryotic cells  1-10m diameter. Each cell typically
contains 2000 mitocondria = 20% cell volume, but number
reflects metabolic activity of the cell.
Mitochodrial DNA is independent of the DNA found in the cell
nucleus & is inherited from the mother (only egg gives
cytoplasm where mitochondria located). Self replication.

Structure – composed of inner and outer membranes composed

of phospholipid bilayer & proteins. The 2 membranes have
different properties and there are distinct compartments within
each mitochondrion. Smooth & rough ER.
1. The intermembrane space - space between the outer and
inner membranes
2. The cristae space - formed by infoldings of the inner
membrane
3. The matrix - space within the inner membrane

Outer mitochondrial membrane contains…

1. Porins - permeable to molecules  5000 daltons.
2. Mitochodrial membrane transport proteins – transport larger molecules by active transport
3. Enzymes

Inner mitochondrial membrane – contains over 100 different polypeptides with a high protein to phospholipid ratio
(3:1). It is highly impermeable and has a membrane potential. It has numerous cristae which SA. The proteins have 4
different functions…
1. Oxidation reactions of the respiratory chain Details of oxidative phosphorylation, cytochromes & electron
transport
2. ATP synthase – produces ATP in the matrix
3. Transport proteins - regulate the passage of metabolites into and out of the matrix.
4. Protein import machinery

Chemiosmotic hypothesis

Metabolic Processes Integrative role in production of energy from CHO, fat + protein metabolism
The matrix contains hundreds of enzymes, ribosomes, tRNA, DNA and the enzymes major functions include…
1. Oxidation of pyruvate
2. Oxidation of fatty acids
3. Citric acid cycle
Other functions
1. Programmed cell death
2. Cellular proliferation
3. Regulation of the cellular oxidation reduction state Drug metabolism
4. Heme synthesis
5. Steroid synthesis
 6. Thermoregulation – mitochondrial uncoupling due to thermoregin in brown fat metabolism
7. Calcium store

Functions can be specific to different cell types e.g. detoxification of ammonia in the liver.
Mutations of genes regulating mitochondrial function  mitochodrial diseases.

1991 Write short notes on the Endoplasmic Reticulum

Endoplasmic reticulum – an organelle found in all eukaryotic cells that is an interconnected network of tubules,
vesicles & cisternae.
Structure – very similar to the plasma membrane. It is an extensive membrane network of cisternae (sac like
structures) held together by the cytoskeleton. The phospholipid membrane encloses a cisternal space (or lumen) from
the cytosol.

Functions - vary greatly depending on the exact type of endoplasmic reticulum and the type of cell in which it resides.
1. Protein – translation, folding, glycosylation & disulfide bond formation (stabilises many proteins)
2. Protein transport - either to the cell membrane or to the golgi apparutus to be exocytosed from the cell
3. Calcium sequestration
4. Production & storage – glycogen, steroids, other macromolecules

Types of Endoplasmic Reticulum

1. Rough endoplasmic reticulum – surface is studded with ribosomes which bind to the ER once it begins to
synthesize a protein destined for sorting. The membrane bound vesicles shuttle proteins between the rough ER & the
Golgi apparatus.
2. Smooth endoplasmic reticulum - involved in several metabolic processes: synthesis of lipids, metabolism of
carbohydrates, calcium concentration, attachment of receptors on cell membrane proteins. In some cells there are
dilated areas like the sacs of rough endoplasmic reticulum. The network of smooth endoplasmic reticulum allows
increased surface area for the action or storage of key enzymes and the products of these enzymes.
3. Sarcoplasmic reticulum – a specialised type of smooth ER found in striated muscle. Has protein bound to its
membranes and drifting within the lumen. Its function is to store and pump calcium ions.

Protein synthesis 2

C. To explain mechanisms of transport of substances across cell membranes including diffusion,

facilitated diffusion, primary active transport and secondary active transport
Forces producing movement of substances across semipermeable membranes

Transport across cell membranes 2

1. Exocytosis
2. Endocytosis
3. Diffusion
4. Facilitated diffusion
5. Primary active transport
6. Secondary active transport

 Exocytosis
Process by which secretory granules fuse to the cell membrane & then the area of fusion breaks down, leaving the
contents on the cell exterior. Requires Ca2+, docking proteins & energy.

 Endocytosis - The reverse of exocytosis. Can be

mediated by cell surface receptors e.g. clathrin.
Phagocytosis – engulfment of bacteria or dead tissue by cells. The
material makes contact with the cell surface, which invaginates
around it. It is then pinched off creating a vacuole & leaving the
cell membrane intact.
Pinocytosis – the same process but involving solutions.
  Diffusion 2 – movement of a substance down its electrochemical gradient, resulting from spontaneous
movement of its constituent particles.
According to Ficks Law.

Transport proteins
Transmembrane proteins that form ions channels or transport substances like
glucose, urea & amino acids. Even water which diffuses, is supplemented
throughout the body with water channels. Some channels are continuously open,
others are gated e.g. ligand, voltage or mechanostretch gated. Some are carriers
that bind ions & other molecules, then change their configuration and swap the
bound molecule from one side to the other.

 Facilitated diffusion - when carriers move molecules in the

direction of the electrical or chemical gradient and no energy is
required. E.g. glucose transporter.

 Active transport 2: primary & secondary active transport

Primary active transport – when a carrier moves molecules against their
electrical or chemical gradient. This requires energy almost exclusively provided
by the hydrolysis of ATP most of these carriers are ATPases. They can be
uniports (transport 1 substance), symports (transport >1 substance in the same
direction) or antiports (exchange 2 substances).
Secondary active transport – when a carrier moves molecules by coupling its
transport to Na+ which is traveling down its electrical or chemical gradient.

93B3 Briefly describe role of intercellular tight junctions  

Tight junctions (zonula occludens) – formed between cells (epithelial & endothelial) whose membranes fuse to form
an impermeable barrier to fluid. Occludin proteins & junctional
adhesion molecule join the cytoskeletons of the adjacent cells.
Regulation - Tight junctions selectively open and close in response to
various signals both inside and outside of cells. This allows the passage
of large molecules or even entire cells across the tight junction barrier.
Function
1. Hold cells together
2. Preserves transcellular transport by blocking the movement of
integral membrane proteins between the apical and basolateral
cell surfaces. This allows specialized functions of each surface
to be maintained e.g. receptor-mediated endocytosis at the
apical surface & exocytosis at the basolateral surface.
3. Controls substance transport through cells - prevents passage
of molecules and ions through the space between cells 
materials must enter cells in order to pass through the tissue.
Important in BBB + distal convoluted tubule.

Gap junctions - connect the cytoplasm of two cells.

One Gap junction is composed of two connexons (or
hemichannels) which connect across the intercellular
space. At gap junctions, the intercellular space narrows
from 25nm to 3nm and connexons in the membrane of
each cell are lined up with one another.
Allow
1. Direct electrical communication between cells
2. Chemical communication between cells via 2nd
messengers
3. Passage of molecules < 1,000 Daltons. Large
biomolecules e.g. nucleic acids + proteins
cannot pass.
Where: virtually all tissues of the body. Particulary important in cardiac muscle - the signal to contract is passed
through the gap junctions allowing cells to contract in unison. Not present in motile cells e.g. sperm, RBCs.

Physiology of intercellular communication

There are 3 general types of intercellular communication. The chemical messengers involved are amines, amino acids,
steroids, polypetides, lipids & pyrimidine nucleotides.
1. Neuronal across synaptic junctions
2. Endocrine
3. Paracrine or autocrine

D. To explain the Gibbs-Donnan Effect

Gibbs Donnan equilibrium 3
The effect of impermeable charged particles on one side of a membrane (e.g. negatively charged proteins) on the
distribution of freely permeable charged particles (e.g. positively charged K + ions & negatively charged Cl- ions). The
distribution of ions on either side of the membrane is effected by the electrical gradient produced by the proteins, as
well as their own concentration gradient.

The Gibbs-Donnan effect is a name for the behavior of charged particles near a semipermeable membrane to
sometimes fail to distribute evenly on either side of the membrane. The usual cause is the presence of a different
charged substance that is unable pass through the membrane and is thus creating an uneven electrical charge.

E. To outline the role of cellular receptors and the function of secondary messengers within the cell
Mechanisms by which chemical messengers act

Extracellular ligands are called “first messengers” whereas intracellular mediators are called “second messengers”.
Second messengers bring about changes in cellular function by altering enzyme function, triggering exocytosis,
altering transcription of various genes. When activated many of the membrane receptors initiate release of secondary
messengers via G-proteins, the secondary messengers activate protein kinases (enzymes that catalyse the
phosphorylation of tyrosine or serine residues in proteins) or initiate phosphorylation of intracellular proteins.

 Cellular receptors
LIGAND GATED ION CHANNELS
Synaptic transmitters “ligands” – ACh, serotonin, GABA & excitatory aa’s (glycine, aspartate, glutamate) – act on a
receptor to increase transmembrane conductance of an ion & thereby altering electrical potentiation across the
membrane.

Acetocholine receptors - muscarinic & nicotinic. Cholinergic receptors

Type Location Structural feature Postreceptor mechanism

M1 CNS neurons, sympathetic 7 transmembrane segments, IP3, DAG cascade
postganglionic neurons, some G-protein linked
presynaptic sites
M2 Myocardium, smooth muscle, some 7 transmembrane segments, Inhibition of cAMP, K+
presynaptic sites G-protein linked channel activation
M3 exocrine glands, vessels (smooth 7 transmembrane segments, IP3, DAG cascade
muscle & endothelium) G-protein linked
NN postganglionic neurons, some Pentamer. Na+/K+ depolarising ion
presynaptic sites 2,, +  subunits channel
NM skeletal muscle end plates & subunits. Na+/Ca2+/K+ depolarising
ion channel

 Nicotinic receptors - transmembrane polypeptides whose subunits form a cation selective ion channel.
Involved in fast synaptic transmission.
History – called nicotinic because the alkaloid nicotine
stimulates them.
Structure - Glycoprotein with 5 subunits: 2 alpha & a beta,
gamma + delta.
Mechanism - Receptor extends through the cellular membrane
creating a channel that allows ions to flow down a concentration
gradient. When 2 molecules bind to the  subunits a channel opens which allows inward Na+ & Ca2+ flow and
outwards K+ flow.
Time – occurs in milliseconds. This rapidity is crucial in moment-to-moment transfer of information across synapse.
Sites & modulation
Postganglionic cells in all autonomic ganglia – anticholinesterases (neostigmine)
Skeletal muscles endplates - DNMB (suxamethonium), NDNMB
Some CNS neurons.

 Gamma-Aminobutyric Acid Receptors Role of GABA receptors in the CNS

GABA is the major inhibitory neurotransmitter & 1/3 of all synapses are responsive to GABA in the CNS. GABA
receptors are found in supraspinal interneurons and are divided into 2 types…

1. GABAA – receptors open chloride channels.

Location - Almost exclusively on postsynaptic nerve endings in the CNS.
Mechanism - Increased transmembrane chloride conductance 
hyperpolarisation of the postsynaptic cell membrane & functional
inhibition of the postsynaptic neuron.

Structure - large macromolecule with separate binding sites for

benzodiazepines, barbiturates and alcohol. All 3 can act on the same
receptor to produce synergistic effects.

Agonist – muscimol
Antagonist – biculline
Modulators - Anaesthetics (benzos, barbiturates, propofol, etomidate) +
ETOH. Enhance GABA mediated inhibition by increasing GABA affinity
for receptors (dissociation) and augment the chloride conductance that is
gated by these receptors. At high doses barbiturates can directly open
chloride channels, benzodiazepines cannot.

2. GABAB – coupled to G-proteins & either inhibit Ca2+ channels or activate K+ channels.
Location - increased concentration in the cerebellum.
Agonist - antispasmodic baclofen.

LIGAND REGULATED TRANSMEMBRANE ENZYMES

Receptors consisting of an extracellular hormone binding domain & a cytoplasmic enzyme
domain. They are connected by a hydrophobic segment that crosses the lipid bylayer.
Hormones - insulin, ANP & epidermal growth factor.
Enzymes – tyrosine kinase, serine kinase or a guanylyl cyclase
Mechanism – tyrosine kinase - when a ligand binds the receptor conformation changes
bringing together tyrosine kinase enzyme domains which become enzymatically active &
phosphorylate eachother & tyrosine residues on signalling proteins.

CYTOKINE RECEPTORS
Many growth factors (insulin like, platelet,
epidermal, nerve, etc) bind to a receptor with a
single membrane spanning domain that activates
tyrosine kinase which autophosphorylates itself and
ultimately leads to the production of transcription
factors that alters gene expression.
Similar to ligand regulated transmembrane
receptors except the enzyme is not intrinsic to the
receptor molecule. E.g. Growth hormone activates
janus tyrosine kinase (JAK) which phosphorylates
signal transducer & activator transcription (STAT)
proteins to alter gene transcription
Ligands – GH, erythropoietin, interferon, etc
Mechanism – when a ligand binds the 2 JAKs
become active & phosphorylate the tyrosine
residues on the receptor which binds 2 STATs
(signal transducers & activators of transcription) which are then phosphoryated by JAK. The 2 STATs attach to each
others tyrosine phosphates dissosociate & travel to the nucleus where they regulate gene transcription.

CYTOPLASMIC RECEPTORS - GENE ACTIVE RECEPTORS

Corticosteroids, mineralocorticoids, sex steroids, vitamin D & thyroid
hormones bind to specific DNA sequences (response elements) near a
gene to stimulate transcription of it.
1. Lag period (30mins-several hours) – synthesis of new proteins takes
time
2. Prolonged effects (hours-days) post [nil] agonist – due to slow
turnover of enzymes & proteins which can remain active in the cell.

E.g. Glucocorticoids – at rest the glucocorticoid receptor is bound to a

heat shock protein which prevents DNA-binding & transcription
activating domains of the receptor from folding into their functionally
active conformations. When glucocorticoids bind the hsp90 is released &
the activated receptor initiates transcription of target genes.

 Second messengers
Second messenger - an intracellular chemical substance that carries a signal from the intracellular domain of a
transmembrane receptor. They amplify & regulate the signal.

 cAMP – Cyclic Adenosine Monophosphate

Mediates…
-catecholamines – CHO & fat breakdown, HR + contractility
PTH – Ca2+ homeostasis
FSH & corticotrophin – regulation of adrenal & sex hormone production
Relaxation of smooth muscle

Mechanism – G proteins stimulate catalytic adenylate cyclase to produce

cAMP. cAMP stimulates cAMP-dependent protein kinases consisting of a
regulatory dimer & 2 catalytic chains. cAMP binds to the regulatory
dimer which releases active catalytic chains. They diffuse through the
cytoplasm + nucleus where they phosphorylate the cAMP-responsive
element binding protein (CREB) which acts as a transcription factor to
increase the transcription of a number of genes. Or phosphorylate proteins
i.e. transfer phosphate from ATP to substrate proteins e.g. enzymes
changing their conformation & activity
Specificity – depends on the particular cells protein substrates available
for the cAMP-dependent protein kinases.
Termination – enzymatic degradation of the cyclic nucleotide to 5’-AMP
by phosphodiesterase & dephosphorylation of kinase substrates.

 Ca2+ & phosphoinositides (IP3 & DAG)

Mediates…via G-proteins or receptor tyrosine kinases
ACh @ muscarinic receptors, Angiotensin, Catecholamines @ 1-adrenoceptors, Platelet activating factor, Serotonin,
Vasopressin @ V1 receptors

Mechanism - G-proteins or receptor tyrosine kinases stimulate phospholipase C which splits PIP 2 into diacylglycerol
& inositol-triphosphate ( PIP2  IP3 & DAG).

DAG stays in the membrane & activates the calcium sensitive protein kinase C.
IP3 diffuses through the cytoplasm & triggers Ca2+ release from internal storage vesicles into the cytoplasm.
Elevated cytoplasmic Ca2+ promotes binding of Ca2+ to calmodulin which regulates enzyme activity (including Ca 2+
dependent protein kinases).
Termination - Ca2+ is pumped away, IP3 is dephosphorylated.

 cGMP – Cyclic Guanosine Monophosphate

Mediates…
ANP + NO - Vascular smooth muscle cells relaxation
Intestinal mucosa
Mechanism – ligands attach to cell surface receptors & active guanylyl cyclase to produce cGMP. cGMP stimulates
cGMP-dependent protein kinases
Termination – enzymatic degradation of the cyclic nucleotide & dephosphorylation of kinase substrates.

EFFECTOR SYSTEMS
 Intracellular calcium
intracellular Ca2+ activates calcium binding proteins which activate a
number of protein kinases. Many second messengers act by
intracellular Ca2+, either from intracellular stores or through ion
channels.

 G-proteins – see below

Inducible enzyme systems

F. To outline the sources of energy available to cells through metabolic processes

H. To describe the role of G proteins

00B11 Describe the structure and function of G proteins 50%
04B15 Describe the mechanism of action of G-proteins in the cell 60%
97B2 47%

Guanine Nucleotide Binding Proteins - intermediaries in cell communication for multiple classes of drugs. They are
universal transducers that amplify intracellular signalling & regulate receptors.

Signalling system has 3 components and is unidirectional

1. Cell surface receptor (7-transmembrane or serpentine)
2. Conformational change  activation of G-protein on
cytoplasmic side of the plasma membrane
3.  change in activity of an effector element.

Structure – heterotrimeric with 3 subunits ().

Mechanism - The agonist activates the receptor which causes GDP

release, allowing GTP to bind. When the GTP attaches to the  subunit,
the +  subunits dissociate. This causes a conformational change and
allows the G-protein to regulate activity of an effector enzyme system or
ion channel (usually the  subunit, but sometimes the  units can
activate ion channels). The enzyme system can be activated or inhibited
& the ion channel can open or close. The signal is terminated when GTP
is hydrolysed to GDP & the system returns to its basal unstimulated state.

Examples of the large superfamily of G-protein receptors include

adrenergic, opioid, muscarinic cholinergic, dopamine & histamine
receptors. They relay signals for over 1000 receptors.
Gstimulatory - -adrenoceptors  stimulated adenylate cyclase cAMP
Ginhibitory - -opioid receptor  opening of K+ channels.
Golfactory - stimulated adenylate cyclase cAMP
Go – brain neurotransmitters (not yet specifically identified
Gq – ACh @ muscarinic receptors, serotonin phospholipase C 
ionisal triphosphate, diacylglycerol & cytoplasmic Ca2+
Gt – photons in rod + cone cells - cGMP

Signal Amplification – NA may only bind -adrenoceptors for a few

milliseconds, however the stimulation of adenylate cyclase depends on the
longevity of Gs activation, which may be for 10+seconds.

Prolonged or repeated exposure to ligands causes desensitisation of receptor

(regulates G-protein linked receptors) – during primary exposure, reversible
with 2nd exposure to agonist after several minutes