THE EFFECTS OF ISOPRENALINE AND A NEW p‐SYMPATHOMIMETIC AMINE UPON SPONTANEOUS ACTIVITY, DIASTOLIC DEPOLARIZATION AND PLATEAU HEIGHT IN CARDIAC PURKINJE FIBRES

Grabowski, Władysław; Lüttgau, Hans-Christoph; Schulze, J.

doi:10.1111/j.1476-5381.1978.tb07794.x

Cited by 11 publications

(2 citation statements)

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“…Such a separation between inotropic actions and effects on time-topeak force might suggest that the two phenomenon are not related. It has been shown, for example, that the effect of isoproterenol to enhance the rate of automaticity in canine cardiac Purkinje fibers involves a different receptor interaction than does the effect of isoproterenol to increase the amplitude of the action potential plateau (Grabowski et al, 1978). Alternatively, the increase in time-to-peak force seen with 3 nM isoproterenol might result from an a-adrenergic action of the amine superimposed on its more familiar /?-adrenergic action, aadrenergic agonist actions of isoproterenol have been reported in canine cardiac Purkinje fibers (Rosen et al, 1977), cat nictitating membrane (Trendelenburg, 1974), and mosquito antennae (Nijhout and Martin, 1978).…”

Section: Discussionmentioning

confidence: 99%

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

Wiggins¹

1981

Circulation Research

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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...

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Section: Discussionmentioning

confidence: 99%

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

Wiggins¹

1981

Circulation Research

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“…Grabowski, Luttgau & Schultze, 1978) than to values reported for effects on processes related to the Purkinje fibre pace-maker current (Tsien, 1974;cf. Rosen, Hordef, Ilvento & Danilo, 1977;Grabowski et al 1978).…”

Section: Discussionmentioning

confidence: 99%

Noradrenaline hyperpolarizes cells of the canine coronary sinus by increasing their permeability to potassium ions.

Boyden¹,

Cranefield²,

Gadsby³

1983

The Journal of Physiology

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SUMMARY1. The mechanism ofthe noradrenaline-induced hyperpolarization was investigated in small strips of coronary sinus tissue mounted in a fast-flow system.2. The recorded hyperpolarization was negligibly small in response to 10 nmnoradrenaline but was maximal at 10/SM (average amplitude 23 mV, in 4 mM-K solution). The hyperpolarization was unaffected by 1 /SM-phentolamine but was abolished by 10 /uM-propranolol and so is presumably mediated via fl-adrenoceptors.3. The noradrenaline-induced hyperpolarization became smaller when the extracellular K concentration ([K]0) was raised or when the extracellular Na concentration was lowered.4. These results are consistent with two general mechanisms: noradrenaline might cause hyperpolarization by stimulating the Na/K pump to generate more outward current, as previously suggested for other cell types. Alternatively, noradrenaline might lower the permeability ratio, PNa/PK, by reducing the permeability coefficient for Na (PNa) and/or increasing that for K (PK).5. The noradrenaline-induced hyperpolarization is not diminished during exposure to 5 ,uM-acetylstrophanthidin, or to K-free solution, or to K-free solution containing acetylstrophanthidin. We conclude that the hyperpolarization does not reflect enhanced electrogenic pump activity. 6. Conductance measurements using two micro-electrodes in very small preparations revealed that, like the muscarinic agonist carbachol, noradrenaline caused an increase in membrane slope conductance. Steady-state current-voltage curves obtained in the presence of noradrenaline, in the presence of carbachol, and in the absence of both drugs all crossed each other at about the same level of membrane potential. During the maintained injection of sufficiently large hyperpolarizing current, application of either noradrenaline or carbachol causes depolarization instead of hyperpolarization.7. The cross-over or 'reversal' potentials of current-voltage curves, determined with and without the drugs, vary with [K]0 approximately as does the K equilibrium potential calculated assuming the intracellular K concentration to be 155 mm. We conclude that, like carbachol and acetylcholine, noradrenaline causes a specific increase in the K permeability of coronary sinus cells.

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Epinephrine and the pacemaking mechanisms at plateau potentials in sheep cardiac Purkinje fibers

Pappano

Carmeliet

1979

Pflugers Arch - Eur J Physiol

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1. In 1.35 mM [K+]0, sheep cardiac Purkinje fibers depolarized to about -40 mV. Whereas some fibers oscillated spontaneously at plateau potentials, others could be made to oscillate when polarized by intracellular currents. Pacemaker activity at plateau potentials (-50 to 0 mV) was distinct from that caused by the iK2 pacemaker at more negative potentials (-60 to -100 mV). 2. Epinephrine induced spontaneously occurring action potentials and increased pacemaker activity in depolarized Purkinje fibers. The ED50 for the positive chronotropic effect of epinephrine was about 5 x 10(-7) M. This concentration is similar to that reported for the effect of epinephrine on plateau amplitude (Carmeliet and Vereecke, 1969) and the slow inward current (isi, Reuter, 1974). 3. In voltage clamp experiments, epinephrine, increased the magnitude of isi and of an outward plateau current, ixi. It is concluded that epinephrine effects pacemaking at plateau potentials by increasing isi and without shifting the voltage dependence of these currents. The onset of pacemaker activity by epinephrine was preceded by membrane depolarization that results from an inward shift of the steady-state current-voltage relation. This current may flow through isi channels that are activated but not completely inactivated.

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THE EFFECTS OF ISOPRENALINE AND A NEW p‐SYMPATHOMIMETIC AMINE UPON SPONTANEOUS ACTIVITY, DIASTOLIC DEPOLARIZATION AND PLATEAU HEIGHT IN CARDIAC PURKINJE FIBRES

Cited by 11 publications

References 20 publications

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

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

Noradrenaline hyperpolarizes cells of the canine coronary sinus by increasing their permeability to potassium ions.

Epinephrine and the pacemaking mechanisms at plateau potentials in sheep cardiac Purkinje fibers

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