Differential contributions of Ca2+-activated K+ channels and Na+/K+-ATPases to the generation of the slow afterhyperpolarization in CA1 pyramidal cells

In many types of CNS neurons, repetitive spiking produces a slow afterhyperpolarization (sAHP), providing sustained, intrinsically generated negative feedback to neuronal excitation. Changes in the sAHP have been implicated in learning behaviors, in cognitive decline in aging, and in epilepto-genesis. Despite its importance in brain function, the mechanisms generating the sAHP are still controversial. Here we have addressed the roles of M-type K+ current (I-M), Ca2+-gated K+ currents (I-Ca(K)'s) and Na+/K+-ATPases (NKAs) current to sAHP generation in adult rat CA1 pyramidal cells maintained at near-physiological temperature (35 degrees C). No evidence for I-M contribution to the sAHP was found in these neurons. Both I-Ca(K)'s and NKA current contributed to sAHP generation, the latter being the predominant generator of the sAHP, particularly when evoked with short trains of spikes. Of the different NKA isoenzymes, alpha(1)-NKA played the key role, endowing the sAHP a steep voltage-dependence. Thus normal and pathological changes in alpha(1)-NKA expression or function may affect cognitive processes by modulating the inhibitory efficacy of the sAHP.