Pharmacological separation of charge movement components in frog skeletal muscle

Abstract

1. Charge movements to small 10 mV steps superimposed upon a wide range of closely spaced depolarizing voltage-clamp pulses were studied in frog skeletal muscles under different pharmacological conditions in hypertonic solutions.2. In control fibres, capacitance was strongly voltage-dependent, especially between potentials of -60 and -20 mV, confirming earlier work. There was a sharp increase in capacitance at around -50 mV. The dependence of non-linear charge on potential was asymmetrical and saturated at around 25 nC/muF.3. The presence of tetracaine abolished the ;hump' in the non-linear transients, which became simple monotonic decays. The dependence of capacitance upon potential was reduced. The maximum available amount of non-linear charge fell to 10 nC/muF.4. The presence of lidocaine abolished both the ;hump' as well as the monotonic part of the non-linear transients. This resulted in capacitance falling with depolarization from -85 mV.5. Comparing the steady-state properties of the non-linear charge under the different pharmacological conditions made it possible to deduce empirically the following components:(i) A lidocaine-resistant component (q(alpha)), which was responsible for the fall in observed capacitance with depolarization from the control voltage.(ii) A component resistant to tetracaine yet abolished by lidocaine (q(beta)). This possesses quasi-exponential kinetics, and a maximum charge of about 20 nC/muF.(iii) A component abolished by both lidocaine and tetracaine (q(gamma)), which possesses a maximum charge of 15 nC/muF. This has complex kinetics, and its steep dependence upon voltage resembles the potential-dependence of the development of tension in skeletal muscle.