pH modulation of currents that contribute to the medium and slow afterhyperpolarizations in rat CA1 pyramidal...

We examined the effects of changes in pH(o) and pH(i) on currents contributing to the medium and slow afterhyperpolarizations (mI(AHP) and sI(AHP), respectively) in rat CA1 neurones. Reducing pH(o) from 7.4 to 6.7 inhibited mI(AHP) and sI(AHP) whereas increasing pH(o) to 7.7 augmented mI(AHP) and, to a greater extent, sI(AHP). The ability of changes in pH(o) to modulate mI(AHP) reflected changes in the Ca(2+)-activated K(+) current, I(AHP), and a Co(2+)- and XE991-resistant component of mI(AHP), but not the muscarine-sensitive current, I(M). In the presence of 1 microM TTX and 5 mM TEA, low pH(o)-evoked reductions in sI(AHP) were associated with reductions in Ca(2+)-dependent depolarizing potentials; because neither effect was attenuated when internal H(+) buffering power was raised by including 100 mm tricine in the patch pipette, the actions of reductions in pH(o) to inhibit sI(AHP) and, possibly, I(AHP) in large part appear to reflect a low pH(o)-dependent decrease in Ca(2+) influx. In contrast, the effects of high pH(o) to augment mI(AHP) and sI(AHP) were associated with relatively small increases in Ca(2+) potentials but were significantly attenuated by 100 mM internal tricine, indicating that a rise in pH(i) consequent upon the rise in pH(o) was largely responsible. The possibility that changes in pH(i) could act to modulate mI(AHP) and sI(AHP), independently of changes in Ca(2+) influx, was also suggested by experiments in which pH(i) was lowered at a constant pH(o) by the external application of propionate or by the withdrawal of HCO(-)(3) from the perfusing medium. Lowering pH(i) at a constant pH(o) had little effect on Ca(2+) potentials but inhibited mI(AHP) and, to a greater extent, sI(AHP), effects that were attenuated by 100 mM internal tricine. Together, the results indicate that changes in pH(o) and pH(i) modulate mI(AHP) and sI(AHP) in rat CA1 neurones and suggest that, depending on the direction of the pH(o) change, the sensitivities of the underlying currents to changes in Ca(2+) influx and/or pH(i) may contribute to the effects of changes in pH(o) to modulate mI(AHP) and sI(AHP).