Myofilament-based relaxant effect of isoprenaline revealed during work-loop contractions in rat cardiac trabeculae.

Abstract

In cardiac muscle, beta-adrenergic stimulation increases contractile force and accelerates relaxation. The relaxant effect is thought to be due primarily to stimulation of Ca(2+) uptake into the sarcoplasmic reticulum (SR), although changes in myofilament properties may also contribute. The present study investigated the contribution of the myofilaments to the beta-adrenergic response in isolated rat cardiac trabeculae undergoing either isometric or work-loop contractions (involving simultaneous force generation and shortening) at different stimulation frequencies (range 0.25-4.5 Hz). SR-dependent effects were eliminated by treatment with ryanodine (1 microM) and cyclopiazonic acid (30 microM). In isometric contractions during SR inhibition, isoprenaline increased the force but did not alter the time course of the twitch. In contrast, in work-loop contractions, the positive inotropic effect was accompanied by a reduced diastolic force between beats, most apparent at higher frequencies (e.g. diastolic stress fell from 58.6 +/- 5.5 to 28.8 +/- 5.8 mN mm(-2) at 1.5 Hz). This relaxant effect contributed to a beta-adrenoceptor-mediated increase in net work and power output at higher frequencies, by reducing the amount of work required to re-lengthen the muscle. Consequently, the frequency for maximum power output increased from 1.1 +/- 0.1 to 1.6 +/- 0.1 Hz. We conclude that the contribution of myofilament properties to the relaxant effect of beta-stimulation may be of greater significance when force and length are changing simultaneously (as occurs in the heart) than during force development under isometric conditions.