MECHANICAL STRETCH INCREASES INTRACELLULAR CALCIUM-CONCENTRATION IN CULTURED VENTRICULAR CELLS FROM NEONATAL RATS

We investigated the effects of mechanical stretch on intracellular cal cium concentration ([Ca2+](i)) of cultured neonatal rat ventricular ce lls using microfluorometry with fura-2. Myocytes were cultured on lami nin-coated silicon rubber and stretched by pulling the rubber with a m anipulator Myocytes were either mildly stretched (to less than 115% of control length) moderately so (to 115%-125% of control length), or ex tensively (to over 125% of the control length). ''Quick stretches'' (a ccomplished within 10s) of moderate to extensive intensities produced a large transient increase of [Ca2+](i) in the early phase of stretch (30s-2 min), followed by a small but sustained increase during the lat e phase of stretch (5-10 min). The initial transient increase in [Ca2](i) after the ''quick stretch'' was preserved in the presence of gall opamil (10(-7) M) or ryanodine (10(-5) M), but was absent in Ca2+-free medium or in the presence of gadolinium (10(-7) M). The late or stead y state [Ca2+](i) increase was observed in the presence of gadolinium, gallopamil, or ryanodine but was abolished in Ca2+-free medium. A ste ady-state increase in [Ca2+](i) was also evoked by ''slow stretch'' in which cells were slowly pulled to the final length within 1-2 min. As the presence of external Ca2+ was indispensable, increased trans-sarc olemmal Ca2+ influx appears to be involved in both initial and steady- slate increases in [Ca2+](i). The initial increase in [Ca2+](i) after the ''quick stretch'' can be attributed to the activation of gadoliniu m-sensitive, stretch-activated channels.