title: Mechanical stress stimulates phospholipase C activity and intracellular calcium ion levels in neonatal rat cardiomyocytes.
abstract: To investigate how mechanical stress is sensed by cardiomyocytes and translated to cardiac hypertrophy, cardiomyocytes were subjected to stretch while measuring phospholipase C (PLC) and phospholipase D (PLD) activities and levels of intracellular calcium ions ([Ca2+]i) and pH. In stretched cardiomyocytes, PLC activity increased 2-fold after 30 min, whereas PLD activity hardly increased at all. Mechanical stress induced by prodding or by cell stretch increased [Ca2+](i)by a factor 5.2 and 4, respectively. Gadolinium chloride (stretch-activated channel blocker) attenuated the prodding-induced and stretch-induced [Ca2+](i)rise by about 50%. Blockade of ryanodine receptors by a combination of Ruthenium Red and procaine reduced the [Ca2+](i)rise only partially. Diltiazem (L-type Ca2+ channel antagonist) blocked the prodding-induced [Ca2+](i)rise completely, and reduced the stretch-induced [Ca2+](i)rise by about 50%. The stretch-induced [Ca2+](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 role. The stretch-induced rise in [Ca2+](i)in cardiomyocytes is most probably caused by [Ca2+](i)influx through L-type Ca2+ channels and stretch-activated channels, leading to Ca2+-induced Ca2+ -release from the SR via the ryanodine receptor.
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Ruwhof
authors.forename: J T
authors.initials: JT
authors.lastname: van Wamel
authors.forename: L A
authors.initials: LA
authors.lastname: Noordzij
authors.forename: S
authors.initials: S
authors.lastname: Aydin
authors.forename: J C
authors.initials: JC
authors.lastname: Harper
authors.forename: A
authors.initials: A
authors.lastname: van der Laarse
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D006332:Cardiomegaly / Q000209:etiology; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004110:Diltiazem / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000378:metabolism; D005682:Gadolinium / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism; D011343:Procaine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012430:Ruthenium Red / Q000494:pharmacology; D013314:Stress, Mechanical; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000779:Anesthetics, Local; D000893:Anti-Inflammatory Agents; D002121:Calcium Channel Blockers; D016895:Culture Media, Serum-Free; D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D012430:Ruthenium Red; D011343:Procaine; D005682:Gadolinium; D010738:Type C Phospholipases; D010739:Phospholipase D; D004110:Diltiazem; C038958:gadolinium chloride; D002118:Calcium