Activation kinetics of the slow afterhyperpolarization in hippocampal CA1 neurons

The activation of the slow afterhyperpolarization (sAHP) in CA1 neurons was studied using whole-cell recordings in the presence of inhibitors of the fast and medium-duration AHPs. The amplitude of the slow afterhyperpolarization current (IsAHP) increased as a function of duration and magnitude of the depolarizing voltage pulse reflecting graded increases in Ca2+ influx through voltage-dependent Ca2+ channels. Therefore, the time constant for activation, tau(max), determined from a family of IsAHPs as a function of pulse duration, was voltage dependent decreasing several-fold within the range of -20 to 20 mV and was dependent on extracellular [Ca2+]. The IsAHP displayed a pronounced rising phase that was well fit by a single exponential with a time constant, tau(rise), that was invariant of pulse duration, voltage, IsAHP amplitude, or external [Ca2+] and was significantly slower than the tau(max). In current clamp, the magnitude of the sAHP increased with the number of evoked action potentials, yet tau(rise) of the sAHP was invariant of action potential number and was similar to the tau(rise) of the IsAHP recorded in voltage-clamp. The results suggest that there are two components to the development of the IsAHP, a rapid, voltage- and Ca2+-dependent step, the magnitude and rate of which reflects the voltage dependence of the Ca2+ channels, that triggers a second rate-limiting, voltage-independent process that dictates the slow IsAHP rise kinetics.