Actions of sympathomimetic amines on the Ca2+ transients and contractions of rabbit myocardium: reciprocal changes in myofibrillar responsiveness to Ca2+ mediated through alpha- and beta-adrenoceptors.

Abstract

The effects of sympathomimetic amines on Ca 2+ transients and isometric contractions were assessed in isolated rabbit papillary muscles in which multiple superficial cells had been microinjected with the calcium-sensitive bioluminescent protein aequorin. In the presence of /3-adrenoceptor blockade, the a-receptor agonist phenylephrine increased both the amplitude of the aequorin signals and the force of contraction in a concentration-dependent manner. However, the maximum increase i n the aequorin signals was less than 10% of that produced by the /3-receptor agonist isoproterenol, while the maximum increase in force of contraction produced by a-stimulation was about 50% of that elicited via /3-adrenoceptors. For a given increase in the force of contraction, stimulation of a-adrenoceptors produced much less change in the amplitude of the aequorin signals than did elevation of the extracellular Ca 2+ concentration; we interpret this to mean that the positive inotropic effect of a-adrenoceptor stimulation is in large part the result of an increase 1 in myofibrillar sensitivity to Ca 2+ . Stimulation of a-adrenoceptors produced little change or a slight decrease i n the duration of the aequorin signal and an increase in the duration of contraction, while stimulation of /3-adrenoceptors significantly decreased the time to peak and duration of both the aequorin signals and the contractions. For a given level of inotropic effect, high concentrations of isoproterenol often increased the aequorin signals more than did elevations of Ca 2+ , which is consistent with other evidence that the cyclic AMP-dependent phosphorylation of troponin I leads to a decrease in myofibrillar Ca 1+ sensitivity. However, concentrations of isoproterenol that did not produce evidence of this sort of desensitization also abbreviated the contractions much more than they did the aequorin signals. This suggests that the traditionally accepted mechanisms -a decrease in the Ca 2+ affinity of troponin C and an acceleration of Ca uptake by the sarcoplasmic reticulum -may not be sufficient to account for the actions of/3-receptor stimulation on the time course of contraction. In the absence of blocking agents, the naturally occurring catecholamines norepinephrine, epinephrine, and dopamine appear to influence the function of the rabbit papillary muscle through both a-and /3-adrenoceptors. Dopamine has a relatively greater effect on a-adrenoceptors than the other catecholamines. (Circulation Research

Cardiovascular effects of the novel Ca2+‐sensitiser EMD 57033 in pigs at rest and during treadmill exercise

“…An alternative explanation could be that EMD 57033 increased Ca 2+ responsiveness via an a-adrenergic receptor dependent mechanism (Endoh & Blinks, 1988;Terzic et al, 1992), so that with increasing exercise levels the progressively greater a-adrenergic receptor stimulation resulted in near maximal increments of myo®lament Ca 2+ responsiveness. As a result EMD 57033 could then have been unable to produce a further increase in Ca 2+ responsiveness via this mechanism.…”

“…The contribution of PDE III inhibition to the actions of these compounds during treadmill exercise was evaluated by studying the e ect of these agents after pretreatment with b-adrenergic receptor blockade. Finally, to exclude the possibility that the EMD 57033-induced increase in Ca 2+ responsiveness was mediated by a-adrenoceptors (Endoh & Blinks, 1988;Terzic et al, 1992), we studied the e ects of EMD 57033 on left ventricular performance at rest and during treadmill exercise in the presence of combined a-and b-adrenergic blockade.…”

The effects of cocaine on intracellular Ca2+ handling and myofilament Ca2+ responsiveness of ferret ventricular myocardium

“…Light signals were recorded with a photomultiplier by means of a light collecting apparatus of a design described by Blinks (1982). In order to obtain a satisfactory signal-to-noise-ratio, it was usually necessary to average successive signals ( (Kamaya et al, 1977;Baker & Schapira, 1980;Endoh & Blinks, 1988). Therefore, the potential for interaction of cocaine and aequorin was tested in vitro by use of the basic method and calibration device described by Endoh & Blinks (1988).…”

The Mechanism of Increasing Ca2+ Responsiveness by .ALPHA.1-Adrenoceptor Stimulation in Rat Ventricular Myocytes.

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It has been reported that ␣ 1 -adrenoceptor stimulation increases contraction with or without a significant change in the peak of Ca 2ϩ transient, and an increase in the Ca 2ϩ responsiveness of the contractile element is considered to be one of the possible mechanisms [1,2]. The increase in the Ca 2ϩ responsiveness of the contractile element by ␣ 1 -adrenoceptor stimulation is explained by intracellular alkalinization or phosphorylation of the contractile elements or both, but the relative contribution of the two mechanisms is still unclear owing to controversy in experimental results [3][4][5][6].

For the assessment of Ca 2ϩ responsiveness, a phase-plane loop (trajectory), obtained by measuring the relation between the intracellular Ca 2ϩ transient and cell shortening in a single isolated myocyte loaded with a fluorescent dye, has been widely used [7].

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