Modulation of sodium channel activity in frog ventricular cells by guanidyl-side armed cyclam.
The mechanism underlying the Na channel blocking action of guanidyl-side armed cyclam (G-cyclam) was studied using conventional patch-clamp methods. G-cyclam applied to the cytoplasmic surface of the membrane reduced the amplitude of single Na channel currents without inducing a flickering block. This effect was enhanced by depolarization and was fully reversible upon washout of the drug. The relationship between the concentration of G-cyclam and the reduction of unitary current could be expressed mathematically assuming one-to-one stoichiometry. During maximal suppression of the single channel current by G-cyclam approximately 40% of the current remained. Low concentration of G-cyclam (3 x 10(-4) M) prolonged, while higher concentration (3 x 10(-3) M) shortened the mean open time suggesting the involvement of two processes in the Na channel blocking action of this agent. It appears that low concentration of G-cyclam induce rapid and frequent transition between open and less conductive state resulting in a reduced current, and higher concentration make the channel nonconductive with slower single channel kinetics.
Yakehiro
M
M
Department of Physiology, School of Medicine, Hiroshima University, Japan.
D000818:Animals; D004563:Electrochemistry; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D066298:In Vitro Techniques; D011892:Rana catesbeiana; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism
D006571:Heterocyclic Compounds; D015222:Sodium Channels; C024560:cyclam