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Inhibition of the calcium channel by intracellular protons in single ventricular myocytes of the guinea‐pig.
Author(s) -
Kaibara M,
Kameyama M
Publication year - 1988
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1988.sp017268
Subject(s) - conductance , chemistry , patch clamp , biophysics , intracellular , calcium channel , calcium , physics , biochemistry , biology , receptor , organic chemistry , condensed matter physics
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.