Involvement of Na+/Ca2+ exchanger in catecholamine-induced increase in intracellular calcium in cardiomyocytes.
Although sarcolemmal (SL) Na+/Ca2+ exchanger is known to regulate the intracellular Ca2+ concentration ([Ca2+]i), its involvement in catecholamine-induced increase in [Ca2+]i is not fully understood. To gain some information in this regard, isolated rat cardiomyocytes were treated with different agents, which are known to modify Ca2+ movements, in the absence or presence of a beta-adrenoceptor agonist, isoproterenol, and [Ca2+]i in cardiomyocytes was determined spectrofluorometrically with fura-2 AM. Treatment with isoproterenol did not alter [Ca2+]i in quiescent cardiomyocytes, whereas the ATP (purinergic receptor agonist)-induced increase in [Ca2+]i was significantly potentiated by isoproterenol. Unlike ryanodine and cyclopiazonic acid, which affect the sarcoplasmic reticulum function, SL L-type Ca2+ channel blockers verapamil and diltiazem, as well as a SL Ca2+-pump inhibitor, vanadate, caused a significant depression in the isoproterenol-induced increase in [Ca2+]i. The SL Na+/Ca2+ exchange blockers amiloride, Ni2+, and KB-R7943 also attenuated the isoproterenol-mediated increase in [Ca2+]i. Combination of KB-R7943 and verapamil showed additive inhibitory effects on the isoproterenol-induced increase in [Ca2+]i. The isoproterenol-induced increase in [Ca2+]i in KCl-depolarized cardiomyocytes was augmented by low Na+; this augmentation was significantly depressed by treatment with KB-R7943. The positive inotropic action of isoproterenol in isolated hearts was also reduced by KB-R7943. These data suggest that in addition to SL L-type Ca2+ channels, SL Na+/Ca2+ exchanger seems to play an important role in catecholamine-induced increase in [Ca2+]i in cardiomyocytes.
Saini
Harjot K
HK
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, 351 Tache Ave., Winnipeg, Manitoba, Canada R2H 2A6.
Tripathi
Onkar N
ON
Zhang
Shetuan
S
Elimban
Vijayan
V
Dhalla
Naranjan S
NS
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D009532:Nickel / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000502:physiology*; D013890:Thiourea / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D019831:Sodium-Calcium Exchanger; D000584:Amiloride; D009532:Nickel; D000255:Adenosine Triphosphate; D011433:Propranolol; D014700:Verapamil; D013890:Thiourea; D007545:Isoproterenol; D002118:Calcium