Kinetics of acetylcholine-activated cation channel blockade by the calcium antagonist D-600 in Aplysia neurons

Cell Mol Neurobiol. 1983 Dec;3(4):329-44. doi: 10.1007/BF00734714.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcholine / pharmacology*
  • Animals
  • Aplysia
  • Calcium / metabolism
  • Dose-Response Relationship, Drug
  • Gallopamil / pharmacology*
  • Ganglia / drug effects
  • Ion Channels / drug effects*
  • Kinetics
  • Membrane Potentials / drug effects
  • Neurons / drug effects
  • Receptors, Cholinergic / drug effects
  • Synaptic Transmission / drug effects*
  • Verapamil / pharmacology*

Substances

  • Ion Channels
  • Receptors, Cholinergic
  • Gallopamil
  • Verapamil
  • Acetylcholine
  • Calcium