Effects of lidocaine alone and in combination with tetraethylammonium on the maximum upstroke velocity in guinea-pig papillary muscles.

Effects of 18.5 mumol/l lidocaine on the Vmax in the absence and presence of 10 mmol/l tetraethylammonium chloride (TEA), which specifically prolongs the action potential duration with little effects on Vmax, were studied in guinea-pig papillary muscles in a 10 mmol/l K+ Tyrode solution. The frequency-dependent reduction of Vmax was significantly increased at high frequencies (3 and 4 Hz) in the presence of lidocaine plus TEA. A simulation study was performed under the assumption that lidocaine interacts with open, inactivated and resting sodium channels and that TEA specifically prolongs the inactivated state, and a reasonable fit to the experimental Vmax changes was obtained. There were no significant differences between the effects of lidocaine alone and lidocaine plus TEA on the tonic blocks, time constants and zero-time intercepts of reactivation process of Vmax. The F-test shows that these reactivation processes in all preparations examined are described sufficiently well by monoexponential functions, that is, under the assumption of the linear relationship between available sodium conductance and Vmax. The finding that a nonlinear model does not significantly improve the fit indicates the possibility that the nonlinearity may not be prominent under the present experimental conditions.