[Potential-dependent interaction of chemical reagents with the sodium channel gating mechanism in a nerve fiber]

Abstract

Effect of two water-soluble carbodiimides (WRC) and Woodward's reagent K (RK) on gating in sodium channels of nodal membrane was examined. The WRC treatment (pH 4.8-5.2) at holding potential from -80 to -100 mV resulted in a considerable slowing down of activation and inactivation processes, and rendered the gating machinery less sensitive to membrane potential changes. Effective charge of activation (Zef) determined from limiting logarithmic slope of activation curve at potentials where channels just begin to open was reduced by the factor of 1.7. The same treatment but at zero holding potential did not reduce Zef, and changed other parameters of gating function to a less degree. RK at high negative holding potentials induced changes in properties of gating machinery similar to those induced by WRC at zero potential. RK effects were less potential-dependent than those of WRC. The results suggest that gating machinery of sodium channel incorporates at least two types of carboxyl groups. The first type: "mobile", play the role of gating particles; during depolarization they move from the surface into the membrane causing opening or inactivation of the channel. The second type: "immobile", is always exposed to the external solution regardless of the channel state.