title: Can Ca entry via Na-Ca exchange directly activate cardiac muscle contraction?
abstract: Developed twitch tension and action potentials were recorded in rabbit ventricular muscle in physiological saline at 30 degrees C stimulated at 0.5 Hz. Addition of 5 microM nifedipine to block Ca entry via Ca channels almost abolished twitches (to 2.5 +/- 0.7%, S.E.M., n = 10 of control). This suggests that under normal conditions Ca entry via Na-Ca exchange is insufficient to activate contractions. However, when muscles are first exposed to 4 microM acetylstrophanthidin to elevate [Na]i the same exposure to nifedipine only partially suppresses twitches (to 59 +/- 12% of the original control). This suggests that when [Na]i is elevated, Ca entry via the Na-Ca exchange may be adequate to partially activate contraction. From this result it is not clear whether Ca entry via Na-Ca exchange is sufficient to activate contraction directly or whether sarcoplasmic reticulum (SR) Ca release is required. When these experiments were carried out in the presence of 5 to 10 mM caffeine or 100 nM ryanodine similar results were obtained. That is, nifedipine still abolished contractions in the presence of caffeine or ryanodine (to 3.8 +/- 0.3% and 1.3 +/- 0.4%, respectively), but only partially inhibited contractions in the presence of caffeine + acetylstrophanthidin (to 21 +/- 5%) or ryanodine + acetylstrophanthidin (10 +/- 2%). Thus, it appears that even in the absence of a functional SR and with Ca current blocked, Na-Ca exchange might bring sufficient Ca into the cell to activate appreciable contractions, but only when [Na]i is elevated. Action potential duration is decreased by nifedipine and acetylstrophanthidin and is further decreased when nifedipine is added on top of acetylstrophanthidin. If this Ca entry is by an electrogenic 3 Na: 1 Ca exchange, Ca entry will be favored at more positive membrane potentials. If the action potential were not so abbreviated with these drugs, Na-Ca exchange might bring in more Ca and activate additional tension.
authors.affiliation: Division of Biomedical Sciences, University of California, Riverside 92521.
authors.forename: D M
authors.initials: DM
authors.lastname: Bers
authors.forename: D M
authors.initials: DM
authors.lastname: Christensen
authors.forename: T X
authors.initials: TX
authors.lastname: Nguyen
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology*; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D011817:Rabbits; D012433:Ryanodine / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger; D013327:Strophanthidin / Q000031:analogs & derivatives / Q000494:pharmacology; D016276:Ventricular Function
chemical_list: D002352:Carrier Proteins; D019831:Sodium-Calcium Exchanger; D012433:Ryanodine; D002110:Caffeine; D013327:Strophanthidin; D009543:Nifedipine; C004681:acetylstrophanthidin; D002118:Calcium