Relationships between calcium and pH in the regulation of the slow afterhyperpolarization in cultured rat hippocampal neurons.

The Ca2+-dependent slow afterhyperpolarization (AHP) is an important determinant of neuronal excitability. Although it is established that modest changes in extracellular pH (pHo) modulate the slow AHP, the relative contributions of changes in the priming Ca2+ signal and intracellular pH (pHi) to this effect remain poorly defined. To gain a better understanding of the modulation of the slow AHP by changes in pHo, we performed simultaneous recordings of intracellular free calcium concentration ([Ca2+]i), pHi, and the slow AHP in cultured rat hippocampal neurons coloaded with the Ca2+- and pH-sensitive fluorophores fura-2 and SNARF-5F, respectively, and whole cell patch-clamped using the perforated patch technique. Decreasing pHo from 7.2 to 6.5 lowered pHi, reduced the magnitude of depolarization-evoked [Ca2+]i transients, and inhibited the subsequent slow AHP; opposite effects were observed when pHo was increased from 7.2 to 7.5. Although decreases and increases in pHi (at a constant pHo) reduced and augm...