Actions of verapamil on the excitability of cultured neurones

Applications of relatively high concentrations of verapamil (0.5-1.0 mM) to cultured spinal cord or dorsal root ganglion neurones blocked both calcium (Ca) and sodium (Na) action potentials. They also depolarized these neurones and caused a voltage-dependent reduction of input conductance (measured under current clamp). The depolarization and apparent reduction of input conductance evoked in spinal cord neurones by L-aspartic acid appeared to be potentiated by coapplications of verapamil. Lower concentrations (maximum 100 microM) of verapamil blocked identified Ca action potentials without depolarizing neurones or changing their input conductance. This Ca antagonist provided only limited selectivity in cultured neurones. Voltage clamp of cultured spinal cord neurones demonstrated that high concentrations of verapamil (0.5-5.0 mM) can reduce outward currents (leakage and rectification). Inward currents evoked with single applications of L-aspartic acid were not potentiated by verapamil and thus potentiations recorded under current clamp can be attributed to depression of outward currents. The reduction of voltage-dependent outward currents (rectification) by verapamil improved resolution of the voltage-dependent inward current activated by L-aspartic acid.