Physiology and Pharmacology
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| Basic mechanism of action potential generation | Local depolarisation opens voltage gated Na channels. Na influx causes depolarisation which opens more Na channels in a positive feedback loop. Channels then inactivate and delayed rectifier K channels open. K efflux begins repolarisation
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| What is threshold | The voltage at which an action potential is triggered. Once Na+ influx exceeds background K+ efflux. If depolarised below this membrane will return to resting. If depolarised above Na channels will open and membrane will continue to depolarise
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| Current flow via passive diffusion | Cells contain electrolytes that can carry ions through the axon, so current can flow like any charged ion. However this is not a possible mechanism as current can leak out the axon via resting membrane conductance, so the current gets weaker along
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| Length constant | Length constant = square root(rm/ri)
This means the length of the axon that the signal will decline by half.
Rm = membrane resistance per unit axon
Ri = internal resistance per unit axon
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| Time constant | T = Rm.Cm
Means the time taken for the membrane potential to be changed
Rm = membrane resistance per unit area of membrane
Cm = membrane capacitance per area of membrane
This depends on membrane resistance
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| Combining length and time constants | If by passive diffusion - along the axon due to current leaking out (length constant) signal declines. Response rises slower as current decreases (time constant)
This means it cannot be by passive diffusiom
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| Action potential propagation in unmyelinated axons | NA influx triggers depolarisation. Current flows to adjacent region depolarising it. This opens Na channel in these areas, generating a new action potential. The action potential is regenerated along the axon. This can be mediated by any ion.
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| Refractory period | The time following one action potential during which another cannot be generated (absolute) or when the threshold for another AP is higher (relative). The area of an axon behind an action potential enters a refractory period due to inactivation of channel
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| Local circuits in impulse propagation | Open ion channels allow Na in, with outwards leak of charge completing the local circuit down the axon and along the outer surface. This moves in forward (orthodromic) and backwards (antidromic) directions. An AP only generated forwards.
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| Effect of local circuits on surface potential | Result in changes to surface potential. This allows electrical activity of neurons to be measure using extracellular electrodes. We can measure changes in surface potential and record the events caused by movement of ions e.g. ECG
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| Evidence for local circuits - Hodgkin | Depolarisation caused at A, with a strong action potential seen (10 mV). A block is present between A and B. B records a weaker AP (1-2mV). Moving along the axon local currents get weaker, resulting in weaker AP due to local current flow
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| Factors governing conduction velocity | Rate of charge entry (current) through active patch of membrane
Spread of local currents (depends on membrane length constant). Further movement = faster AP
Speed of membrane depolarisation by local current flow (depends on membrane time constant)
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| How length constant effects conduction velocity | Governs the length of an axon ahead of the impulse that can be depolarised to threshold. Long length constant means more distant areas of membrane ahead can be depolarised to threshold, so increases conduction velocity
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| How size affects conduction velocity | Internal resistance is inversely dependant upon axon cross sectional area.
Membrane resistance is inversely dependant on axon circumference.
Length constant is proportional to square root (a/2) so bigger axons conduct faster
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| Effect of size on time constant | No effect - decrease in membrane potential is cancelled out by a corresponding increase in membrane capacitance
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| How are axons myelinated | Axon is wrapped in many layers of Schwann cells.
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| Effect of myelination on length constant | Membrane resistance is increased by myelination, as the membrane is less leaky
Increasing Rm increases the membrane length constant
Increasing length constant increases conduction velocity
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| Effect of myelination on time constant | Increasing Rm will slow the time constant, decreasing conduction velocity. However, Schwann cells increase membrane capacitance as each layer acts as a separate capacitor. By decreasing Rm and increasing Cm myelination has ne effect on the time constant
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| How do impulses propagate in a myelinated nerve | An action potential can only be generated at a node of Ranvier. Local currents travel further to depolarise the membrane, generating APs at each node. This makes the AP seem to jump along the neuron, known as Saltatory conduction
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| Effect of Na+ channel density on conduction velocity | In myelinated neurons, voltage gated Na channels are packed at high density at the nodes of Ranvier. High packing density gives a large inward current, with gives a high conduction velocity.
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| 3 factors affecting conduction velocity | Time constant
Length constant
Magnitude of the Na influx
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| Evidence for Saltatory conduction - Tasaki and Takeuchi | Neuron with 2 nodes separated by a block placed in a bath. When electrically stimulated a small depolarisation is produced at beginning and end with nothing between. When a third node is placed halfway through the block, the AP is detected in the block
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| Comparing effect of axon diameter in myelinated and non-myelinated neurons | In myelinated neurons there is a linear relationship. In non myelinated neurons conduction velocity is proportional to the square root of the radius. Myelinated neurons out perform non-myelinated except at very small diameters
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| Role of myelinated neurons 2-20 um diameter | Alpha - proprioception, somatic motor
Beta - touch, pressure
Gamma - motor to muscle spindles
Delta - pain, cold, touch
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| Role of myelinated neurons less than 3 um diameter | preganglionic autonomic
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| Role of unmyelinated neurons 0.3-1.2 um in diameter | Dorsal root - pain, temperature, mechanoreceptor
Sympathetic - Postganglionic sympathetic
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| Diseases involving decreased conduction velocity | Multiple sclerosis - inflammatory
Guillain-Barre syndrome - autoimmune often following Campylobacter jejuni infection
Diphtheria - in about 10% of cases
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