Mechanical stress stimulates phospholipase C activity and intracellular calcium ion levels in neonatal rat cardiomyocytes

To investigate how mechanical stress is sensed by cardiomyocytes and transl ated to cardiac hypertrophy, cardiomyocytes were subjected to stretch while measuring phospholipase C (PLC) and phospholipase D (PLD) activities and l evels of intracellular calcium ions ([Ca2+](i)) and pH. In stretched cardiomyocytes, PLC activity increased 2-fold after 30 min, wh ereas PLD activity hardly increased at all. Mechanical stress induced by pr odding or by cell stretch increased [Ca2+](i) by a factor 5.2 and 4, respec tively. Gadolinium chloride (stretch-activated channel blocker) attenuated the prodding-induced and stretch-induced [Ca2+](i) rise by about 50%. Block ade of ryanodine receptors by a combination of Ruthenium Red and procaine r educed the [Ca2+](i) rise only partially. Diltiazem (L-type Ca2+ channel an tagonist) blocked the prodding-induced [Ca2+](i) rise completely, and reduc ed the stretch-induced [Ca2+](i) rise by about 50%. The stretch-induced [Ca 2+](i) rise was unaffected by U73122, an inhibitor of PLC activity. Stretch did not cause cellular alkalinization. In conclusion, in cardiomyocytes, PLC and [Ca2+](i) levels are involved in the stretch-induced signal transduction, whereas PLD plays apparently no ro le. The stretch-induced rise in [Ca2+](i) in cardiomyocytes is most probabl y caused by Ca2+ influx through L-type Ca2+ channels and stretch-activated channels, leading to Ca2+-induced Ca2+-release from the SR via the ryanodin e receptor. (C) 2001 Harcourt Publishers Ltd.