Both physiological and pathological neuronal events, many of which elevate
intracellular [Ca2+], can produce changes in intracellular pH of between 0.
15 and 0.5 U, between pH 7.3 and 6.8. N-type Ca2+ channels, which are intim
ately involved in exocytosis and other excitable cell processes, are sensit
ive to intracellular pH changes. However, the pH range over which N-type Ca
2+ channels are sensitive, and the sensitivity of N-type Ca2+ channels to s
mall changes in intracellular pH, are unknown. We studied the influence of
intracellular pH changes on N-type calcium channel currents in dorsal root
ganglion neurons, acutely isolated from 14-day-old chick embryos. Intracell
ular pH was monitored in patch-clamp recordings with the fluorescent dye, B
CECF, and manipulated in both the acidic and basic direction by extracellul
ar application of NH4+ in the presence and absence of intracellular NH4+. C
hanges in intracellular pH between 6.6 and 7.5 produced a graded change in
Ca2+ current magnitude with no apparent shift in activation potential. Intr
acellular acidification from pH 7.3 to 7.0 reversibly inhibited Ca2+ curren
ts by 40%. Acidification from pH 7.3 to pH 6.6 reversibly inhibited Ca2+ cu
rrents by 65%. Alkalinization from pH 7.3 to 7.5 potentiated Ca2+ currents
by approximately 40%. Channels were sensitive to pH(i) changes with high in
tracellular concentrations of the Ca2+ chelator, bis-(o-aminophenoxy)-N, N,
N',N'-tetraacetic acid, which indicates that the effects of pH(i) did not
involve a Ca2+-dependent mechanism. These data indicate that N-type Ca2+ ch
annel currents are extremely sensitive to small changes in pH(i) in the ran
ge produced by both physiological and pathological events. Furthermore, the
se data suggest that modulation of N-type Ca2+ channels by pH(i) map play a
n important role in physiological processes that produce small changes in p
H(i) and a protective role in pathological mechanisms that produce larger c
hanges in pH(i).