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Regulation of nerve terminal calcium channel selectivity by a weak acid site.
Metadata
Journalbiophysical journal3.854Date
1979-May
Type
Research Support, U.S. Gov't, P.H.S.
Journal Article
Volume
1979-May / 26 : 329-34
Author
Nachshen DA , Blaustein MP
DoiPMIDMESH
Animals
Biological Transport, Active
Brain
Calcium
Cations, Divalent
Hydrogen-Ion Concentration
Ion Channels
Kinetics
Potassium
Rats
Synaptosomes
Abstract
The effects of low pH, and of alkaline earth cations, were examined on calcium uptake by pinched-off nerve terminals (synaptosomes). This uptake appears to be mediated by voltage-sensitive Ca channels (J. Physiol. 247:617, 1975). Ca uptake was measured in low (5 mM) or high (77 mM) potassium media. The extra uptake promoted by depolarizing (K-rich) media was almost maximal at pH 7.5, and decreased as the pH was lowered. Data relating depolarization-induced 45Ca uptake to pH fit a titration curve with a pKa approximately 6. Experiments in which Ca concentration and pH were both varied indicated that Ca2+ and H+ compete for a common binding site. Inhibition of depolarization-induced 45Ca uptake by the alkaline earth cations was studied to determine the apparent binding sequence for these cations in the Ca channels: Ca greater than Sr greater than Ba greater than Mg. This sequence resembles that observed for block of Ca channels in other preparations. The apparent binding sequence of the alkaline earth cations and the apparent pKa (approximately 6) of the Ca-binding site indicate that the Ca channel is a "high field strength" system. Protonation of a Ca channel binding site could explain the inhibitory effect of low pH on Ca-dependent neurotransmitter release (cf. Del Castillo et al., J. Cell. Comp. Physiol. 59:35, 1962).
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3.9
Biophys Jbiophysical journal
Metadata
LocationUnited States
FromCELL PRESS

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