BETA-ADRENERGIC MODULATION OF MYOCYTE CA2+, MEMBRANE CURRENTS, AND CONTRACTION

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Beta-adrenergic agonists increase the myocardial contraction strength and enhance relaxation. Calcium is a critical agent in the activation and relaxation of contraction in the heart. When calcium binds to the myofilaments, contraction is initiated; when calcium comes off the myofilaments, relaxation occurs. Two possible determinants of relaxation are: (1) the sensitivity of the myofilaments for calcium, and (2) calcium sequestration e.g. by the sarcoplasmic reticulum (SR). The contractile enhancement by beta-adrenergic agonists is due to an increase in the calcium released into the myoplasmic space. Whether beta-adrenergic stimulation specifically abbreviates the cytosolic calcium transient, measured via the calcium indicator aequorin in intact muscle, is controversial. We examined the effect of isoproterenol, 5X10-7M, on cytosolic calcium transient (measured via indo 1 fluorescence 410 nm/490 nm) membrane potential and cell shortening during the twitch (video edge detector) in single rat and guinea pig cardiac myocytes. In guinea pig cell isoproterenol (0.1 uM) increased the peak calcium current 3-fold. The 4-fold larger estimated calcium entry (integrated) area of calcium current) contributes to the estimated augmentation of contraction. The steady state myoplasmic calcium transient rose with 2.7 fold larger rate to a 2.7 fold higher peak and was reached after 65 instead of 300 ms after the start of depolarization. Isoproterenol accelerated the decay of the calcium transient 4.4 fold. Thus, the beta-adrenergic agonist, isoproterenol, not only potentiates the twitch but also leads to more rapid and complete relaxation of the myoplasmic calcium transient under the present conditions. This may account for the accelerated relaxation of contraction.