I NaCa andI Cl(Ca)contribute to isoproterenol-induced delayed afterdepolarizations in midmyocardial cells

Autor: Charlene M. Weigel, Andrew C. Zygmunt, Robert J. Goodrow
Rok vydání: 1998
Předmět:
Zdroj: American Journal of Physiology-Heart and Circulatory Physiology. 275:H1979-H1992
ISSN: 1522-1539
0363-6135
Popis: The contributions of electrogenic sodium/calcium exchange current ( I NaCa), calcium-activated chloride conductance [ I Cl(Ca)], and calcium-activated nonselective cation conductance to delayed afterdepolarizations (DAD) were examined. Nonselective cation channels were absent in canine M cells, since inhibition of I NaCa and I Cl(Ca)eliminated all calcium-activated currents without abolishing cell shortening. After the cells were treated with isoproterenol and ouabain to increase calcium loading, I NaCa was 168 ± 30 × 10−3 pC/pF and I Cl(Ca) was 114 ± 24 × 10−3pC/pF. Transient overlapping inward and outward currents were evoked positive to the chloride reversal potential ( E Cl). Outward current was chloride sensitive, and inward current was blocked by replacement of external sodium with lithium. When E Cl was −50 mV, triggered activity occurred in normal external sodium and persisted after inhibition of I NaCa. Steps to −80 mV revealed oscillating inward currents in normal sodium and chloride, which persisted after inhibition of I NaCa. When E Cl was equal to −113 mV, I Cl(Ca) opposed I NaCa at the resting potential. DAD occurred in normal sodium, and inhibition of outward I Cl(Ca)provoked triggered activity. We conclude that I NaCa represents ∼60% of the total calcium-activated current at resting potentials but that both I NaCa and I Cl(Ca) work in concert to cause DAD in calcium-overloaded cells.
Databáze: OpenAIRE