membrane potential

• measured with intracellular and extracellular electrode
• about -70mV in typical neuron
• varies from -15 to -100mV in all cells
• in neurons called resting potential
• established by ion grandients
• particularly high Na out, high K in due to NaK ATPase
• in relation to ion permeability
• use Nernst to calculate K equilibrium potential in squid axon (-70 mV rp)
• Ko=10, Ki=350
• E=2.303RT/zF (log10 Ko/Ki)= -91mV
• use Nernst to calculate Na equilibrium potential
• E=+55mV
• -> resting potential close to K pot.=> K main determinant=> cell perm. only to K
• slight Na and Cl permeabilities account for the discrepancy

action potential at a single position

• if cell is slightly depolarized ie made less negative (eg -70 to -60)
• return rest is quickly achieved after stimulation is eliminated due to
• diffusion of charge and pump activity
• if cell is depolarized past threshold set by Na channel voltage sensitivity (-50mV)
• Na channels open->Na influx to equilib potential (+55mV)
• Na channels close automatically after 1msec
• K channels open (voltage gated at about 0mV)
• K efflux to equilib potential (-90mV)
• K channels close (due to negative potential)
• K leak current is main permabilty left and resting potential is restored
• Na channels become refractory after closing and cannot be reopened for several msecs
• note that no energy is required once initial gradients are established
• also note that very few ions (compared to total) actually move and thus:
• several thousand APs can take place without any pump activity
• also note that APs are all-or-none because of threshold to opening channels
• local anesthetics block Na channel opening and thus electrical signalling

propogation of action potential

• depolarization usually limited to one end of cell (eg axon hillock)
• Na influx leads to current flow inside cell
• the amount of Na entry from an AP is always enough to depolarize adjacent segments
• these segments go past threshold and their Na channels are opened etc
• speed can be increased by two strategies
• invertebrate cells increase axon diameter
• rate increases w/ sq root of diameter-> marginal speed increases
• due to greater local (intracellular) current diffusion in large axons
• vertebrates myelinate their axons
• high electrical resistance greatly increases local (intracell) current flux
• gaps between myelin (nodes of Ranvier) contain the Na channels
• this produces saltatory conduction
• 120meters/sec is about 20X faster than unmyelinated axon
• MS is a degenerative disease of the myelin sheath
• leads to paralysis

synaptic cleft

• 20-50nm gap between terminal arbor and postsynaptic cell
• signalling occurs as follows
• depol. opens voltage gated Ca channels
• Ca influx changes Cai from 100 nM to 100uM
• Ca promotes membrane fusion and transmitter release
• transmitter diffusion in cleft/ receptor binding
• two type of receptor
• excitatory: Na channel opening-> depol.
• inhibitory: K channel opening-> hyperpol.
• signal lasts about 2 mscec due to:
• transmitter destruction eg AchE
• transmitter reuptake eg transporter (active or facillitated)
• nerve gas blocks AchE-> violent contractions
• cocaine blocks dopamine reuptake (in limbic system causing euphoria)
• Parkinsons can be treated in part by preventing dopamine reuptake because:
• degenerative disease of dopaminergic neurons
• block reuptake-> increase dopamine potential for signaling