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Ca(2+)-signaling in cardiac myocytes: evidence from evolutionary and transgenic models
1Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20007-2197, USA.
Abstract:
Cardiac contraction is regulated by a number of Ca(2+)-mediated processes. Here we consider the effects of modification imposed on the Ca(2+)-signalling mechanism by evolutionary developments and transgenic manipulations. Ca(2+)-signalling appears to be mediated via influx of Ca2+ through the DHP receptor in preference to the Na(+)-Ca2+ exchange protein, and activates the ryanodine receptor and the Ca2+ release from the SR. Here we report on functional consequences of overexpression of the Na(+)-Ca2+ exchanger and calsequestrin. The data does not support a physiological role for the Na(+)-Ca2+ exchanger in signalling Ca2+ release, but can serve to modify ionic currents which determine the duration of the action potential.
Insights
Calcium signaling in cardiac contraction is primarily mediated by the DHP receptor, not the Na(+)-Ca2+ exchanger. Overexpression studies reveal the exchanger influences action potential duration but not Ca2+ release signaling.
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
- Cellular Electrophysiology
Background:
- Cardiac contraction relies on intricate calcium (Ca2+) mediated processes.
- Evolutionary and transgenic modifications impact Ca2+ signaling pathways.
Purpose of the Study:
- To investigate the functional consequences of overexpressing the Na(+)-Ca2+ exchanger and calsequestrin.
- To elucidate the role of the Na(+)-Ca2+ exchanger in cardiac Ca2+ signaling and action potential duration.
Main Methods:
- Functional analysis of transgenic models with altered Na(+)-Ca2+ exchanger and calsequestrin expression.
- Electrophysiological assessments to determine effects on ionic currents and action potential.
Main Results:
- Ca2+ signaling predominantly involves DHP receptors over the Na(+)-Ca2+ exchanger for activating ryanodine receptors and sarcoplasmic reticulum Ca2+ release.
- Overexpression of the Na(+)-Ca2+ exchanger did not support a physiological role in signaling Ca2+ release.
- The Na(+)-Ca2+ exchanger was found to modify ionic currents, influencing action potential duration.
Conclusions:
- The Na(+)-Ca2+ exchanger is unlikely to be a primary physiological mediator of Ca2+ release signaling in the heart.
- The Na(+)-Ca2+ exchanger plays a modulatory role in cardiac electrophysiology by affecting action potential duration.