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

• Published in: American journal of physiology. Heart and circulatory physiology 1998-12, Vol.275 (6), p.H1979-H1992
• Main Authors: Zygmunt, Andrew C, Goodrow, Robert J, Weigel, Charlene M
• Format: Article
• Language: English
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.1998.275.6.H1979

The contributions of electrogenic sodium/calcium exchange current ( I ), calcium-activated chloride conductance [ I ], 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 and I eliminated all calcium-activated currents without abolishing cell shortening. After the cells were treated with isoproterenol and ouabain to increase calcium loading, I was 168 ± 30 × 10 pC/pF and I was 114 ± 24 × 10 pC/pF. Transient overlapping inward and outward currents were evoked positive to the chloride reversal potential ( E ). Outward current was chloride sensitive, and inward current was blocked by replacement of external sodium with lithium. When E was -50 mV, triggered activity occurred in normal external sodium and persisted after inhibition of I . Steps to -80 mV revealed oscillating inward currents in normal sodium and chloride, which persisted after inhibition of I . When E was equal to -113 mV, I opposed I at the resting potential. DAD occurred in normal sodium, and inhibition of outward I provoked triggered activity. We conclude that I represents ∼60% of the total calcium-activated current at resting potentials but that both I and I work in concert to cause DAD in calcium-overloaded cells.