Effects of drugs on acetylcholine-activated ionic channels of internally perfused chick myoballs.
The effects of intracellular application of three compounds - QX314, N-ethylguanidine and N-octylguanidine - on the acetylcholine-activated ionic channels in chick myoballs were examined. Voltage-clamped myoballs were internally perfused using the suction-pipette technique. Changes in the internal ionic environment of myoballs were demonstrated by: (1) alteration of the reversal potential for both acetylcholine-activated ionic currents and voltage-gated sodium currents in a manner predicted by the Goldman-Hodgkin-Katz equation, and (2) elimination of potassium currents after removal of intracellular and extracellular potassium. Ethylguanidine (5 mM) and octylguanidine (5 microM) blocked acetylcholine-induced currents by 83% when applied externally. QX314 (0.5 mM) and octylguanidine (100 microM) had no effect on acetylcholine-induced currents when perfused internally, although in the same cells these compounds caused marked inhibition of voltage-gated sodium currents. Ethylguanidine (10 mM) reduced acetylcholine-induced currents by approximately 20-30% after internal application. It was much less potent from inside than from outside, and the inhibition was not voltage-dependent. We conclude that the internal mouth of the acetylcholine-activated channel must be much more selective with respect to drug binding than is the external channel mouth. Internally applied ethylguanidine may penetrate into the channel beyond the selectivity filter to a drug binding site to cause block.
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000502:physiology*; D000200:Action Potentials; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D002642:Chick Embryo; D006146:Guanidines / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects*; D008012:Lidocaine / Q000031:analogs & derivatives / Q000494:pharmacology; D008564:Membrane Potentials; D009045:Motor Endplate / Q000187:drug effects; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
D006146:Guanidines; D007473:Ion Channels; C012647:QX-314; C015403:octylguanidine; C038594:N-ethylguanidine; D008012:Lidocaine; D000109:Acetylcholine