A significant fraction of calcium transients in intact guinea pig ventricular myocytes is mediated by Na(+)-Ca2+ exchange
Abstract
Ca2+ mobilization elicited by simulation with brief pulses of high K+ were monitored with confocal laser scanned microscopy in intact, guinea pig cardiac myocytes loaded with the calcium indicator fluo-3. Single wavelength ratioing of fluorescence images obtained after prolonged integration times revealed non-uniformities of intracellular Ca2+ changes across the cell, suggesting the presence of significant spatial Ca2+ gradients. Treatment with 20 microM ryanodine, an inhibitor of Ca2+ release from the SR, and 10 microM verapamil, a calcium channel blocker, reduced by 42% and 76% respectively the changes in [Ca2+]i elicited by membrane depolarization. The overall spatial distribution of [Ca2+]i changes appeared unchanged. Ca2+ transients recorded in the presence of verapamil and ryanodine (about 20% of the size of control responses), diminished in the presence of 50 microM 2-4 Dichlorbenzamil (DCB) or 5 mM nickel, two relatively specific inhibitors of the Na+/Ca2+ exchange mechanism. Conversely, when the reversal potential of the Na+/Ca2+ exchange was shifted to negative potentials by lowering [NA+]o or by increasing [Na+]i by treatment with 20 microM monensin, the amplitude of these Ca2+ transients increased. Ca2+ transients e...Continue Reading
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