Inotropic actions of isoproterenol in cat ventricular muscle. Effects of extracellular potassium.

Abstract

SUMMARY The inotropic actions of isoproterenol in cat papillary muscles or trabeculae bathed in a salt solution containing 4 mM KCl were compared to those in similar muscles bathed in a salt solution containing 22 mM KCl. Although isoproterenol evoked the same increase in force of contraction in both groups of muscles, the time course of contraction differed markedly. In muscles bathed in 4 mM KCl, isoproterenol caused a concentration-dependent decrease in time-to-pealt force, but in muscles bathed in 22 mM KCl, isoproterenol caused a concentration-dependent increase in time-to-peak force. These data suggest that ventricular muscle activated by slow response action potentials may utilize a different mechanism of excitation-contraction coupling than do muacles activated by Na-dependent action potentials. Circ Res 49: [718][719][720][721][722][723][724][725] 1981 ISOPROTERENOL and other y3-adrenergic agonists have positive inotropic effects in mammalian myocardium. In the presence of normal extracellular potassium (4 mM), the spectrum of this positive inotropic effect has been well established: isoproterenol increases both force of contraction and the maximum rate of force development while causing an abbreviation of both the time-to-peak force and total contraction time (Scholz, 1980). /3-adrenergic agonists also enhance the slow inward current in potassium-depolarized cardiac fibers (for review, see Cranefield, 1975) and many investigators have made use of this property to induce "slow response" type action potentials in mammalian ventricular muscle. Watanabe and Besch (1974) showed that isoproterenol has a concentration-dependent positive inotropic effect in such "slow response-activated" muscle, and most investigators appear to have assumed that the inotropic actions of isoproterenol are identical in muscles activated by "fast response" and by "slow response" action potentials. However, there have been no systematic studies comparing this activity, and there are isolated observations (see for example, Fig. 4 in Becker et al., 1977) which suggest that, in slow response activated muscle, isoproterenol increases time-to-peak force. I have therefore, reexamined the inotropic actions of isoproterenol in cat ventricular muscle to assess the degree of which the inotropic activities of the drug are altered by extracellular potassium. The results show that the spectrum of inotropic activity Received December S, 1980. acrrpted for publication April 7, 1981. of isoproterenol is markedly dependent on extracellular potassium; in the presence of elevated [K]o, the positive inotropic effect of isoproterenol is strongly dependent on an increase in time-to-peak force. One interpretation of these results is that the mechanism for excitation-contraction coupling changes in the presence of elevated [K] o . A brief report of these results has been published (Wiggins, 1980a).Methods Cats (1.5-3.0 kg, unselected for breed or sex) were obtained from the Hillsborough County (Florida) Animal Control Office and housed in the Vivar...

Voltage-dependent calcium release in guinea-pig cardiac ventricular muscle as antagonized by magnesium and calcium

“…Since a low stimulation frequency secured the absence of a stimulation-dependent sodium load with the ensuing continuous calcium uptake through NaCa exchange, it could be assumed that the calcium stored in the release compartments of the sarcoplasmic reticulum (the junctional SR) had accumulated only from previous activity. In accordance with observations under comparable experimental conditions (16,34), it was found that increased potassium concentration blocks an early contraction component, the amplitude of which is determined by the degree to which the SR had been previously loaded with calcium (20,21). The present results show that the elevated [K+]o does not suppress the early contraction component if sufficiently high stimulation frequencies are used, as evidenced by test contractions elicited shortly after a low frequency contraction.…”

“…Only a slight increase in force remained during the first 100 ms, after which a phasic contraction developed which reached its peak at about 200 ms after the stimulus. Similar observations have been made in high KC1 solutions with guinea-pig papillary muscles in the presence of histamine (16) and with cat papillary muscles in the presence of isoprenaline (34). This indicates that at low contraction frequencies, and especially under Table 1).…”

Effects of selective channel blocking agents on contractions and action potentials in K+‐depolarized guinea‐pig atria

“…The contrasting inotropic actions of quinidine (and Org 6001) on contractions in normal as compared with depolarized atrial preparations raise questions regarding the possible different mechanisms of electromechanical (E-C) coupling in the two situations. Wiggins (1981) has provided strong evidence to suggest that in potassium depolarized cardiac muscle, 'slow' action potentials induced by isoprenaline allow the muscle to utilize calcium directly from extracellular sources for contraction. In contrast, in nondepolarized muscle, with functional fast Na' channels, intracellular calcium stores are ofprimary importance.…”

“…Wiggins (1981) has provided strong evidence to suggest that in potassium depolarized cardiac muscle, 'slow' action potentials induced by isoprenaline allow the muscle to utilize calcium directly from extracellular sources for contraction. In contrast, in nondepolarized muscle, with functional fast Na' channels, intracellular calcium stores are ofprimary importance.…”

Effect of urapidil on the action potentials in the guinea-pig ventricular myocardium

“…Gulch et al [12] showed the effect of urapidil on action potentials in normal Tyrode solution only at concentrations higher than 10 .3 M. They speculated that it had an effect on the slow inward Ca 2+ current because of its suppression of contactile force. Since contractile force of muscle can be influenced not only by the Ca 2+ current, but also by some other mechanisms that affect the stored Ca 2÷ [16], such as the Na ÷ current inhibition through Na÷-Ca 2÷ exchange, and Na÷-K ÷ ATPase inhibition [17][18][19], the information on muscle contraction seems to provide insufficient evidence for suppression of the Ca 2+ current.…”