Potassium currents during the action potential of hippocampal CA3 neurons

Central neurons have multiple types of voltage-dependent potassium channels, whose activation during action potentials shapes spike width and whose activation and inactivation at subthreshold voltages modulate firing frequency. We characterized the voltage-dependent potassium currents flowing during the action potentials of hippocampal CA3 pyramidal neurons and examined the susceptibility of the underlying channel types to inactivation at subthreshold voltages. Using acutely dissociated neurons that permitted rapid voltage clamp, action potentials recorded previously were used as the command voltage waveform, and individual components of potassium current were identified by pharmacological sensitivity. The overall voltage-dependent potassium current in the neurons could be split into three major components based on pharmacology and kinetics during step voltage pulses: I(D) (fast activating, slowly inactivating, and sensitive to 4-aminopyridine at 30 microm), I(A) (fast activating, fast inactivating, and sensitive to 4-aminopyridine at 3 mm), and I(K) (slowly activating, noninactivating, and sensitive to external TEA at 3-25 mm). The potassium current during the action potential was composed of approximately equal contributions of I(D) and I(A), with a negligible contribution of I(K). I(D) and I(A) had nearly identical trajectories of activation and deactivation during the action potential. Both I(A) and I(D) showed steady-state inactivation at subthreshold voltages, but maximal inactivation at such voltages was incomplete for both currents. Because of the major contribution of both I(D) and I(A) to spike repolarization, it is likely that modulation or partial inactivation at subthreshold voltages of either current can influence spike timing with minimal effect on spike width.