Class Note for BME 510 at UA
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Date Created: 02/06/15
Chemical Synaptic Transmission Synaptic structure and function general observations Electrical response of the postsynaptic cell Synaptic current and reversal potential Role of calcium in release Quantal nature of neurotransmitter release Green a neuron with many dendrites ll Figure 11738 part 2 of 2 Molecular Biology of he Cell 4th Edition Relationship between synap c structure and function Recepmmnannels open Na enlers the poslsvnamic cell and vesl39clss lecycle Caz envy causes ves39lcle luslon and xmnsminer veleass Action potentlal in nerve terminal opens Caz channals Prasynaplic actinn poxemlal Presvrlsmir nerve terminal Recapmr Excilalury postsynaptic channel WIGHUBI n mV P 05139 4 s aDIIC 3 cell The neuromuscular junction serves as a favorable model for investigating synaptic m t m structure and function Schwann Iv sheath Acetylcholine Ach released from the presynaptic terminal binds to ligandgated ion channels Ach receptors to trigger a postsynaptic conductance increase Junnnanal fold Vonageaaxed Na39 channel Transport filling fu5Ion anel release W of synaptic 543 M ve5Icles Cnpyrlgm 0 2m sum Scim Ordinarily each action potential in the motor axon causes enough Ach release to evoke an action potential in the muscle fiber However if the preparation is bathed in a low Ca2 solution or is treated with curare the subthreshold excitatory postsynaptic potential EPSP aka endplate potential or EPP is revealed The amplitude of the EFF decreases and its time course increases with distance from the endplate as dictated by the passive properties of the muscle fiber membrane from Fatt and Katz 1951 1 Motor axon Muscle ber 0 1 2 3 4mm End plate milkm m 10 ms 2001 Slnauer Assnclalas Inc With two electrodes it is possible to record the postsynaptic membrane potential and inject constant current to change it The postsynaptic membrane potential is not really clamped Thus the voltage amplitude of the gt EPP can be recorded following motor axon stimulation EPP amplitude is sensitive to membrane potential 39 39 Muscle fiber Em 55 mV Em 0 quot V Restin potential Ex m m g e brane 490 mV 100 mv B Stimulate motor axon WWW 10A meg st Depolarizing synaptic potential at the endplate Inward synaptic current at the end plate Emulate Potential Total snd39nlale current L 4 It is also possible to do a voltageclamp experiment A feedback amplifier is used to inject the current required to m the muscle fiber membrane potential at different command values The endplate current can be measured following nerve stimulation The end plate current varies with postsynaptic membrane potential 30 mV V 30 mv ii 770 mV iii Synaptic current ILA A To v0 age cla mp circuit Microelectrode for measuring Vm amp Outward 200 f O V Inward ll 2 ms From voltage clamp circuit Currentepassing electrode for controlling Vm The endplate current varies linearly with postsynaptic membrane potential except for extreme hyper or depolarizing holding potentials Thus the synaptic conductance is not voltagedependent The reversal potential provides information about ion selectivity from Takeuchi and Takeuchi 1960 pA 100 38 mV 39 22 V 50 3 In l I I l 40 130 100 50 25 50 70 o 750 95 39 o 120 100 O 150 uwxn 5mm quotAsmmalp a 2mm 5mm Manama la1 Singlechannel currents 81 Site of elementary current Wclnsed zoo mi i C Total ionic current in a patch at membrane a rreni Scan of alsmemarv cu 20 ms A 72 5 72 7 2 s Size cl aiemenmy current 512 m DAY 39 gm 100 ms Ach increases the probability of opening for ligandgated AchR channels Patchclamp records reveal singlechannel conductance mean opentime and ion selectivity Membrane B rlpA Polenliai 70 mV i I L VimVi 20 40 80 so quoti J 100 ms No EPP is evoked following nerve stimulation without Ca2 in the bath A puff of Ca2 app ed directly at the endplate region before nerve stimulation allows the EFF to be evoked From Katz and Miledi 1967 Stim puff Recordings from the end plate region reveal spontaneous miniature end plate potentials M EPPs These occur randomly in time without nerve stimulation and are of relatively constant amplitude A Intracellular microelectrode Muscle ber At the same endplate EPPs evoked by nerve stimulation with low Ca2 in the bath are found to be integral multiples of the MEPPs Each trace shows several stimulus trials superimposed From Fatt amp Katz 1951 and Del Castillo amp Katz 1954 The quantal hypothesis holds that neurotransmitter is released at synapses in quantal units A mini represents the spontaneous release of one quantum whereas the normal evoked response consists of many quanta released simultaneously EPSP amplitude equals the number of quanta released quantal content m times the amplitude of each quantum quantal size q VEPSP m X 1 Number of observations The amplitudes of EPPs evoked by nerve stimulation fall into discrete peaks that are integral multiples of the mean MEPP amplitude Del Castillo amp Katz 1954 a u a Number of observations 5 B 02 04 06 08 Amplitude of spontaneous potentials mV VH I I I i I I I I I I I I I I 0 02 04 06 08 10 12 14 16 18 20 22 24 26 28 30 Amplitude of endplate potentials mV anm SInauerAssacimes Inn Slnausr Associates Inc Inhibitory postsynaptic potentials lPSPs ordinarily reverse sign near the resting membrane potential Thus they tend to move the postsynaptic cell away from rather than toward the threshold for action potential generation 3 64 w S g 74 W Tc 2 Q 93 8 82 W O E C E SHIV 2 101 N Time ms o 2001 Sinauer Amalas Inc Comparison of EPSPs and lPSPs The reversal potential represents the membrane potential at which the net synaptic current is zero For EPSPs which ordinarily are due to current flow through ligandgated channels that are permeable to both Na and W the reversal potential is at a membrane potential somewhere between ENal and EK This is usually quite depolarized from the resting membrane potential For lPSPs which ordinarily are due to current flow through ligandgated Cl or K channels the reversal potential is at either ECl or EK which are near the resting membrane potential Action new PM IHNUMWEBIIE awn mill magnum all m 95 Ellmm minty ow rmquot at W dunell In If Na 539 391 quotM r r H39 ihry pun thSPl 11 a I 5 Ifhpmymp cmllmut m bIFSI hmm mmmhmmmd m Cnpyrigli U 21201 Elmier Scienn USA Ml right renewed Consequences of synaptic inhibition An EPSP alone or in summation with other EPSPs may reach threshold and E mm evoke an action potential An IPSP will prevent this by subtracting from the EPSP to move the postsynaptic cell away from threshold Even if a the postsynaptic cell is sitting c RmaMWWWW at the reversal potential for the IPSP any attempt of an EPSP ccccc m to bring the membrane k 1 potential to threshold will be WV thwarted by the inhibitory synaptic current IPSC which ssva k i will usually be in the opposite Eu direction ofthe EPSC and by 5 the shunting action of the 5 W V inhibitory conductance increase V 1
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