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.
Kiss
L
L
Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269, USA.
Korn
S J
SJ
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002614:Chelating Agents / Q000494:pharmacology; D002642:Chick Embryo; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000737:chemistry* / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002614:Chelating Agents; D010455:Peptides; D000644:Quaternary Ammonium Compounds; D004533:Egtazic Acid; D020866:omega-Conotoxin GVIA; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid