Inhibition of the calcium channel by intracellular protons in single ventricular myocytes of the guinea-pig

1. The inhibitory effects of intracellular protons (Hi+) on the L-type Ca2+ channel activity were investigated in single ventricular myocytes of guinea-pigs by using the patch-clamp method in the open-cell-attached patch configuration, where 'run down' of the channel was partially prevente...

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Bibliographic Details
Published in:The Journal of physiology 1988-09, Vol.403 (1), p.621-640
Main Authors: Kaibara, M, Kameyama, M
Format: Article
Language:English
Subjects:
Action Potentials - drug effects
Animals
Barium - physiology
calcium
Calcium - physiology
Calcium Channels - physiology
Guinea Pigs
Heart - physiology
Hydrogen-Ion Concentration
In Vitro Techniques
Kinetics
Protons
Rose Bengal - pharmacology
ventricle
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Summary:1. The inhibitory effects of intracellular protons (Hi+) on the L-type Ca2+ channel activity were investigated in single ventricular myocytes of guinea-pigs by using the patch-clamp method in the open-cell-attached patch configuration, where 'run down' of the channel was partially prevented. 2. Hi+ reduced the unitary Ba2+ current of the Ca2+ channel by 10-20% without changing the maximum slope conductance. 3. Hi+ did not alter the number of channels in patches containing one or two channels. 4. Hi+ markedly reduced the mean current normalized by the unitary current, which gave the open-state probability multiplied by the number of channels in the patch. The dose-response curve between Hi+ and the open-state probability indicated half-maximum inhibition at pHi 6.6 and an apparent Hill coefficient of 1. 5. Hi+ shifted both the steady-state activation and inactivation curves in a negative direction by 10-15 mV, and the effects were reversible. 6. Hi+ did not affect the fast open-closed kinetics represented by the C-C-O scheme, apart from increasing the slow time constant of the closed time. 7. Hi+ increased the percentage of blank sweeps and reduced that of non-blank sweeps resulting in a decreased probability of channel opening. 8. Photo-oxidation with Rose Bengal abolished the reducing effect of Hi+ on the open-state probability (Po) in two out of ten experiments, suggesting the possible involvement of histidine residues in the Hi+ effect. 9. The above results indicate that Hi+ inhibits the Ba2+ current mainly by affecting the slow gating mechanism of the channel.
ISSN:0022-3751
1469-7793
DOI:10.1113/jphysiol.1988.sp017268