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The Journal of Neurophysiology Vol. 81 No. 4 April 1999, pp. 1839-1847
Copyright ©1999 by the American Physiological Society
Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269
Kiss, Laszlo and
Stephen J. Korn.
Modulation of N-type Ca2+ channels by intracellular pH in
chick sensory neurons. 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 7.4 and 6.8. N-type Ca2+
channels, which are intimately involved in exocytosis and other excitable cell processes, are sensitive to intracellular pH changes. However, the pH range over which N-type Ca2+ channels are
sensitive, and the sensitivity of N-type Ca2+ channels to
small 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. Intracellular pH was monitored in patch-clamp
recordings with the fluorescent dye, BCECF, and manipulated in both the
acidic and basic direction by extracellular application of
NH4+ in the presence and absence of intracellular
NH4+. Changes in intracellular pH between 6.6 and 7.5 produced a graded change in Ca2+ current magnitude with no
apparent shift in activation potential. Intracellular acidification
from pH 7.3 to 7.0 reversibly inhibited Ca2+ currents by
40%. Acidification from pH 7.3 to pH 6.6 reversibly inhibited
Ca2+ currents by 65%. Alkalinization from pH 7.3 to 7.5 potentiated Ca2+ currents by approximately 40%. Channels
were sensitive to pHi changes with high intracellular
concentrations of the Ca2+ chelator,
bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid,
which indicates that the effects of pHi did not involve a
Ca2+-dependent mechanism. These data indicate that N-type
Ca2+ channel currents are extremely sensitive to small
changes in pHi in the range produced by both physiological
and pathological events. Furthermore, these data suggest that
modulation of N-type Ca2+ channels by pHi may
play an important role in physiological processes that produce small
changes in pHi and a protective role in pathological mechanisms that produce larger changes in pHi.
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