Interactions of guanidine and a related compound with potassium channels in frog myelinated nerve fibre.
The effects of guanidine and dimethyl guanidine were studied on current- and voltage-clamped nodes of Ranvier, to determine the electrophysiological basis for the guanidine-induced increase in neurotransmitter release. When added to the external solution, guanidine produced positive shifts of K and Na conductance-voltage curves. As a consequence, we observed a decrease of ionic flux through K channels, as well as through Na channels, and the resultant prolongation of the action potential. In addition, guanidine slowed down the time course of K current activation and reduced the percentage of inactivated Na channels. The main effect of guanidine is thus to induce depolarizing shifts of the potential dependence of K and Na channel gating parameters. Guanidine, like divalent cations, may alter the density of fixed negative charges on the outside membrane surface. The results of the action of dimethyl guanidine imply that, in addition to possible unspecific screening of the negative surface charges by cations, some specific interactions are involved. In conclusion, the prolongation of the action potential attributable to the effect of guanidine on external surface charges might contribute to the action of the drug in facilitating transmitter release by allowing the entry of more Ca ions into nerve endings.
Benoit
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Laboratoire de Physiologie cellulaire, URA CNRS 1121, Université Paris sud, Orsay, France.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004594:Electrophysiology; D019791:Guanidine; D006146:Guanidines / Q000494:pharmacology*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D008760:Methylguanidine / Q000031:analogs & derivatives / Q000494:pharmacology; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism; D009412:Nerve Fibers / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D011893:Rana esculenta; D011901:Ranvier's Nodes / Q000187:drug effects / Q000378:metabolism; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism
D006146:Guanidines; D015221:Potassium Channels; D015222:Sodium Channels; D008760:Methylguanidine; C042632:N,N-dimethylguanidine; D019791:Guanidine; D011188:Potassium; D002118:Calcium