DIFFERENT MECHANISMS FOR [CA2-CONCENTRATIONS OF [CA2+](O) IN THE RAT VENTRICULAR MYOCYTE(](I) OSCILLATIONS INDUCED BY CARBACHOL AND HIGH)

1. The purpose of the present study was to explore the different mecha nisms of [Ca2+](i) oscillations induced by high concentrations of eith er carbachol (CCh) or extracellular Ca2+ ([Ca2+](o)). First, we compar ed 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, Sec ond, we studied CCh- and [Ca2+](o)-induced [Ca2+](i) oscillations foll owing either interference with the production of inositol trisphosphat e (IP3), reductions in cytosolic Ca2+ ([Ca2+](i)), inhibition of Ca2influx and Na+-Ca2+ exchange or depletion of Ca2+ from its intracellul ar store, 2. The [Ca2+](i) oscillations induced by CCh were frequent a nd were superimposed on [Ca2+](i) transients in electrically stimulate d cells, whereas those induced by high [Ca2+](o) were occasional and o ccurred in quiescent cells and between [Ca2+](i) transients in electri cally stimulated cells, In both cases, [Ca2+](i) oscillations mere pre ceded by an increase in resting levels of [Ca2+](i), 3. Carbachol-indu ced [Ca2+](i) oscillations were accompanied by an increase in amplitud e and prolongation of the time of decline to 80% of the peak of the [C a2+](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 trea tment with Ni2+ Or ryanodine or ,2-bis(2-aminophenoxy)ethane-N,N,N',N' -tetraacetic acid AM (BAPTA-AM) abolished the [Ca2+](i) oscillations i nduced 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; Liaccelerated the onset of the [Ca2+](i) oscillations induced by CCh, 6, These observations suggest that the mechanisms responsible for the [C a2+](i) oscillations induced by CCh and high [Ca2+](o) are different f rom 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 o f Ca2+ via L-type Ca2+ channels, Na+-Ca2+ exchange, mobilization of in tracellular Ca2+ and IP3 production.