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, τ_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 [Ca ²⁺]. The IsAHP displayed a pronounced rising phase that was well fit by a single exponential with a time constant, τ_rise, that was invariant of pulse duration, voltage, IsAHP amplitude, or external [Ca ²⁺] and was significantly slower than the τ_max. In current clamp, the magnitude of the sAHP increased with the number of evoked action potentials, yet τ_rise of the sAHP was invariant of action potential number and was similar to the τ_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.