Effect of RP 30356 on the fast inward Na current in frog atrial fibres.
The effect of a new drug: RP 30356, on action potential and fast inward Na current of frog atrial fibres was studied using the double sucrose gap voltage clamp technique. The drug (10(-4)M) blocked the action potential without noticeably altering the resting membrane potential. RP 30356 inhibited the fast sodium conductance without changing the selectivity of the Na channel. The time to peak of the inward current was not significantly altered by the drug whereas the rate of the Na current inactivation pi h was slowed. The steady state inactivation membrane potential relationship of the Na system was shifted toward negative membrane potentials by the drug. It was also shown that in Ringer solution the reactivation time constant of the Na system (pi re) was faster at more negative membrane potentials than at more positive ones. The drug increased pi re; the increase was more marked when the membrane was depolarized. The block of Na conductance by the drug was partially removed by increasing the membrane potential to values more negative than -70 mV. The drug did not leave the channel or left it very slowly in the absence of clamp stimulation. The inhibition of the Na conductance by RP 30356 was also frequency-dependent. The data suggest that RP 30356 might be effective in the control of cardiac arrhythmias since it mainly decreased the excitability of depolarized fibres.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects*; D054833:Isoindoles; D008564:Membrane Potentials / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology*; D011893:Rana esculenta; D012964:Sodium / Q000378:metabolism*
D000889:Anti-Arrhythmia Agents; D007211:Indoles; D007473:Ion Channels; D054833:Isoindoles; D011412:Propanolamines; C025215:nofedone; D012964:Sodium