title: Rates and equilibria at the acetylcholine receptor of Electrophorus electroplaques: a study of neurally evoked postsynaptic currents and of voltage-jump relaxations.
abstract: Kinetic measurements are employed to reconstruct the steady-state activation of acetylcholine [Ach] receptor channels in electrophorus electroplaques. Neurally evoked postsynaptic currents (PSCs) decay exponentially; at 15 degrees C the rate constant, alpha, equals 1.2 ms(-1) at 0 mV and decreases e-fold for every 86 mV as the membrane voltage is made more negative. Voltage-jump relaxations have been measured with bath-applied ACh, decamethonium, carbachol, or suberylcholine. We interpret the reciprocal relaxation time 1/tau as the sum of the rate constant alpha for channel closing and a first-order rate constant for channel opening. Where measureable, the opening rate increases linearly with [agonist] and does not vary with voltage. The voltage sensitivity of small steady-state conductances (e- fold for 86 mV) equals that of the closing rate alpha, confirming that the opening rate has little or no additional voltage sensitivity. Exposure to alpha-bungarotoxin irreversibly decreases the agonist-induced conductance but does not affect the relaxation kinetics. Tubocurarine reversibly reduces both the conductance and the opening rate. In the simultaneous presence of two agonist species, voltage-jump relaxations have at least two exponential components. The data are fit by a model in which (a) the channel opens as the receptor binds the second in a sequence of two agonist molecules, with a forward rate constant to 10(7) to 2x10(8) M(-1)s(-1); and (b) the channel then closes as either agonist molecule dissociates, with a voltage-dependent rate constant of 10(2) to 3x10(3)s(-1).
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000200:Action Potentials; D000818:Animals; D002800:Cholinesterase Inhibitors; D004593:Electrophorus / Q000502:physiology; D008564:Membrane Potentials; D009045:Motor Endplate / Q000502:physiology*; D009388:Neostigmine / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000502:physiology*; D010830:Physostigmine / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000502:physiology*; D012964:Sodium / Q000378:metabolism
chemical_list: D002800:Cholinesterase Inhibitors; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D009388:Neostigmine; D012964:Sodium; D010830:Physostigmine; D000109:Acetylcholine