The slow afterhyperpolarization modulates high pH-induced changes in the excitability of rat CA1 pyramidal neurons

Extra- and intracellular recordings from the CA1 region of rat hippocampal slices were employed to examine the role of the slow afterhyperpolarization (sAHP) in modulating the increases in neuronal excitability observed on increasing extracellular pH (pHo) from 7.4 to 7.7. In the majority of experiments, an antidromic conditioning stimulus applied in the presence of D(-)-2-amino-5-phosphonopentanoic acid (D-APV), 6-cyano-7-nitroquinoxaline-2,3-dione disodium salt (CNQX) and bicuculline was employed to elicit a sAHP, and an antidromic test stimulus was applied during the sAHP. At pHo 7.4, a single conditioning stimulus elicited an action potential followed by a sAHP, which in turn inhibited the response to the test stimulus compared with the conditioning stimulus. Increasing the number of action potentials in the conditioning stimulus augmented the sAHP and further inhibited the test response, whereas isoproterenol inhibited the sAHP and prevented the relative inhibition of the test response. At pHo 7.7, a single conditioning stimulus elicited a burst of action potentials followed by a large sAHP, which in turn prevented the test stimulus from eliciting a burst of action potentials and, in extracellular recordings, further increased the inhibition of the test response. The latter effect did not solely reflect a high pHo-induced increase in the conditioning response (and, thus, the subsequent sAHP), but rather involved a more direct effect of high pHo to augment the sAHP. The results indicate that increasing pHo increases the excitability of CA1 neurons to an initial stimulus; however, a high pHo-dependent increase in the sAHP evoked by the initial stimulus limits the response to subsequent stimuli.