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Modulation by stimulation rate of basal and cAMP-elevated Ca2+ channel current in guinea pig ventricular cardiomyocytes
The modulation of L-type Ca2+ current (ICa) by changes in stimulation frequency was investigated in single ventricular cardiomyocytes isolated from guinea pig hearts. Electrical recordings were carried out at 21-25 degrees C and at 33-37 degrees C with the whole-cell patch clamp method, under K(+)-f...
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Lenguaje: | English |
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The Rockefeller University Press
1995
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2229258/ https://www.ncbi.nlm.nih.gov/pubmed/8537815 |
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collection | PubMed |
description | The modulation of L-type Ca2+ current (ICa) by changes in stimulation frequency was investigated in single ventricular cardiomyocytes isolated from guinea pig hearts. Electrical recordings were carried out at 21-25 degrees C and at 33-37 degrees C with the whole-cell patch clamp method, under K(+)-free conditions. A comparison is made between the response to frequency changes for ICa in the basal state and after the application of drugs which elevate the level of adenosine-3',5'- cyclic monophosphate (cAMP) within the cells. Peak basal ICa was reduced with an increase in stimulation rate from 0.5 Hz to 1, 2, 3, 4, or 5 Hz. This frequency-induced reduction of ICa was enhanced by reduced temperature, was unchanged when Na+ or Ba2+ carried the basal Ca2+ channel current, and was greatly enhanced after elevating cAMP levels with forskolin, isoprenaline, or 8-(4-chlorophenylthio)-cyclic AMP. We examined the mechanism of the enhancement of the frequency- induced reduction of ICa by cAMP, and found two conditions which abolished it: (a) application of isoprenaline when Na+ carried the Ca2+ channel current in Ca(2+)-free solution, or (b) application of 3- isobutyl-1-methylxanthine, a broad-spectrum phosphodiesterase inhibitor. It was further shown that an elevation of both ICa and cAMP (induced by isoprenaline), and not an increase of ICa alone (induced by Bay K 8644), is required to produce the extra component of reduction by frequency. It is concluded that Ca2+ entry results in feedback regulation of ICa, through the activation of Ca(2+)-dependent phosphodiesterase(s). This is important in the context of sympathetic stimulation, which produces the companion conditions of an elevated heart rate and increases in cAMP levels and Ca2+ entry. |
format | Text |
id | pubmed-2229258 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1995 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22292582008-04-23 Modulation by stimulation rate of basal and cAMP-elevated Ca2+ channel current in guinea pig ventricular cardiomyocytes J Gen Physiol Articles The modulation of L-type Ca2+ current (ICa) by changes in stimulation frequency was investigated in single ventricular cardiomyocytes isolated from guinea pig hearts. Electrical recordings were carried out at 21-25 degrees C and at 33-37 degrees C with the whole-cell patch clamp method, under K(+)-free conditions. A comparison is made between the response to frequency changes for ICa in the basal state and after the application of drugs which elevate the level of adenosine-3',5'- cyclic monophosphate (cAMP) within the cells. Peak basal ICa was reduced with an increase in stimulation rate from 0.5 Hz to 1, 2, 3, 4, or 5 Hz. This frequency-induced reduction of ICa was enhanced by reduced temperature, was unchanged when Na+ or Ba2+ carried the basal Ca2+ channel current, and was greatly enhanced after elevating cAMP levels with forskolin, isoprenaline, or 8-(4-chlorophenylthio)-cyclic AMP. We examined the mechanism of the enhancement of the frequency- induced reduction of ICa by cAMP, and found two conditions which abolished it: (a) application of isoprenaline when Na+ carried the Ca2+ channel current in Ca(2+)-free solution, or (b) application of 3- isobutyl-1-methylxanthine, a broad-spectrum phosphodiesterase inhibitor. It was further shown that an elevation of both ICa and cAMP (induced by isoprenaline), and not an increase of ICa alone (induced by Bay K 8644), is required to produce the extra component of reduction by frequency. It is concluded that Ca2+ entry results in feedback regulation of ICa, through the activation of Ca(2+)-dependent phosphodiesterase(s). This is important in the context of sympathetic stimulation, which produces the companion conditions of an elevated heart rate and increases in cAMP levels and Ca2+ entry. The Rockefeller University Press 1995-08-01 /pmc/articles/PMC2229258/ /pubmed/8537815 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Articles Modulation by stimulation rate of basal and cAMP-elevated Ca2+ channel current in guinea pig ventricular cardiomyocytes |
title | Modulation by stimulation rate of basal and cAMP-elevated Ca2+ channel current in guinea pig ventricular cardiomyocytes |
title_full | Modulation by stimulation rate of basal and cAMP-elevated Ca2+ channel current in guinea pig ventricular cardiomyocytes |
title_fullStr | Modulation by stimulation rate of basal and cAMP-elevated Ca2+ channel current in guinea pig ventricular cardiomyocytes |
title_full_unstemmed | Modulation by stimulation rate of basal and cAMP-elevated Ca2+ channel current in guinea pig ventricular cardiomyocytes |
title_short | Modulation by stimulation rate of basal and cAMP-elevated Ca2+ channel current in guinea pig ventricular cardiomyocytes |
title_sort | modulation by stimulation rate of basal and camp-elevated ca2+ channel current in guinea pig ventricular cardiomyocytes |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2229258/ https://www.ncbi.nlm.nih.gov/pubmed/8537815 |