Different mechanisms for [Ca2+]i oscillations induced by carbachol and high concentrations of [Ca2+]o in the rat ventricular myocyte

1. The purpose of the present study was to explore the different mechanisms of [Ca2+](i) oscillations induced by high concentrations of either carbachol (CCh) or extracellular Ca2+ ([Ca2+](o)). First, we compared the oscillations induced by CCh at concentrations of 100-300 mu mol/L and [Ca2+](o) (5 mmol/L) in the single rat ventricular myocyte, Second, we studied CCh- and [Ca2+](o)-induced [Ca2+](i) oscillations following either interference with the production of inositol trisphosphate (IP3), reductions in cytosolic Ca2+ ([Ca2+](i)), inhibition of Ca2+ influx and Na+-Ca2+ exchange or depletion of Ca2+ from its intracellular store, 2. The [Ca2+](i) oscillations induced by CCh were frequent and were superimposed on [Ca2+](i) transients in electrically stimulated cells, whereas those induced by high [Ca2+](o) were occasional and occurred in quiescent cells and between [Ca2+](i) transients in electrically stimulated cells, In both cases, [Ca2+](i) oscillations mere preceded by an increase in resting levels of [Ca2+](i), 3. Carbachol-induced [Ca2+](i) oscillations were accompanied by an increase in amplitude and prolongation of the time of decline to 80% of the peak of the [Ca2+](i) transient, while high [Ca2+](o)-induced [Ca2+](i) oscillations were the opposite, 4. A reduction of [Ca2+](o) to 0.1 mmol/L and treatment with Ni2+ Or ryanodine or 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid AM (BAPTA-AM) abolished the [Ca2+](i) oscillations induced by both CCh and high [Ca2+](o), 5, The calcium channel blockers verapamil and nifedipine and inhibitors of phospholipase C (neomycin and U-73122) abolished the [Ca2+](i) oscillations induced by CCh; Li+ accelerated the onset of the [Ca2+](i) oscillations induced by CCh, 6, These observations suggest that the mechanisms responsible for the [Ca2+](i) oscillations induced by CCh and high [Ca2+](o) are different from each other, Other than an increase in extracellular Ca2+ influx as a mechanism common for both CCh- and high [Ca2+](o)-induced [Ca2+](i) oscillations, the CCh-induced [Ca2+](i) oscillations involve influx of Ca2+ via L-type Ca2+ channels, Na+-Ca2+ exchange, mobilization of intracellular Ca2+ and IP3 production.