C. Ruwhof et al., Mechanical stress stimulates phospholipase C activity and intracellular calcium ion levels in neonatal rat cardiomyocytes, CELL CALC, 29(2), 2001, pp. 73-83
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.