Kinetics of acetylcholine-activated cation channel blockade by the calcium antagonist D-600 in Aplysia neurons.
The effects of the calcium channel blocker D-600 on the cation channels activated by acetylcholine (ACh) was studied in voltage-clamped Aplysia neurons by voltage-jump relaxation analysis. D-600 blocked the steady-state ACh current in a highly voltage-dependent manner, the degree of antagonism increasing with membrane hyperpolarization. In the presence of D-600 the current relaxations following hyperpolarizing command steps became biphasic. The time constants of ACh-induced current relaxations (tau f), which approximate the mean channel lifetime, were reduced in a voltage-dependent manner, the degree of reduction of tau f increasing with increasing membrane potential. In addition to the acceleration of tau f, a slow, inverse kinetic component (tau s) of the relaxation appeared in the presence of D-600. The rate of this inverse kinetic component was accelerated either by increasing the agonist or antagonist dose or by increasing the membrane potential. These results suggest that D-600 acts to antagonize the acetylcholine response through a blockade of the open state of the transmitter-activated cation channel. Possible kinetic schemes for this interaction are discussed.
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001048:Aplysia; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005711:Gallopamil / Q000494:pharmacology*; D005724:Ganglia / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D011950:Receptors, Cholinergic / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology*
D007473:Ion Channels; D011950:Receptors, Cholinergic; D005711:Gallopamil; D014700:Verapamil; D000109:Acetylcholine; D002118:Calcium