Calcium conductance and tension in mammalian ventricular muscle

Abstract

Voltage, membrane current and contraction were simultaneously measured in voltage clamp experiments (single sucrose gap) on cat ventricular trabeculae. The pulse programs allowed the determination of the potential dependence of the steady state activation and inactivation as well as the restoration of the calcium-carrying system (slow inward current). 1. The steady state activation variable (d infinity) rose in a sigmoid manner from -50 mV (d infinity nearly 0) to 0 mV (d infinity nearly 1). The experimental values can be described by the function 1/1 + exp [(Vh-V)/S] where half activation (Vh) = -22.5mV and S = 7.6 mV. 2. The steady state inactivation variable (f infinity) declined from 1 at -60mV to 0 at 10mV. The best fit curve is nearly a mirror image of the activation curve with Vh = -28 mV and s = -8.3 mV. 3. The voltage dependence of the (normalized) peak tension was well described by the steady state conductance variables except at potentials positive to +20mV. A "steady state" tension (superimposed on "tonic tension") was found in the potential range where a steady state conductance is predicted by the curves describing steady state activation and inactivation. 5. Following inactivation, the time courses of restoration of the calcium-carrying system and tension were identical. Time courses were exponential with tau = 118 msec at -80 mV, 144 msec at -60 mV, and 198 msec at -40 mV. 6. Two possible models of excitation-contraction coupling in line with the present results are discussed.

Inhibition of myocardial Ca2+ channels by three dihydropyridines with different structural features: potential‐dependent blockade by Ro 18–3981

“…To our knowledge this is the first demonstration of a potential-dependent negative inotropic effect by any DHP-type Ca2+ channel blocking drug. The development of contractile tension in isolated cardiac preparations has been shown to be closely correlated with activation of the inward Ca2" current (Trautwein et al, 1975 This was the case for all three DHPs in the isolated atria experiments. A shift to the left of the concentration-response curves, ranging between 8 and 137 fold at the IC_, level, was observed when the extracellular K+ concentration was elevated from 5.9 to 24 mM.…”

Voltage‐clamp studies of transient inward current and mechanical oscillations induced by ouabain in ferret papillary muscle

“…6A, the phasic twitch has a threshold at or below -40 mV and reaches a maximum with clamp steps to + 10-+ 20 mV; in these experiments a small descending limb was detected (cf. Trautwein, McDonald & Tripathi, 1975). The shape of the phasic tension -voltage curve suggests a correlation with the activation curve for the slow inward current (Beeler & Reuter, 1970b; Trautwein et al 1975).…”

Mechanism of slow discharges of sheep carotid artery.

“…In other respects, the electrical behaviour of the arteries shows some resemblances to that of cardiac muscle. Cardiac muscle like the arteries has a slowly inactivating inward channel able to use Ca, and K channels which can be opened by moderate and closed by larger depolarization (see Weidmann, 1951;Hutter & Noble, 1960;Orkand & Niedergerke, 1964;Niedergerke, Page & Talbot, 1969;Rougier, Vassort, Garnier, Gargouil ;Coraboeuf, 1969; Kohlhardt, Bayer, Krause & Fleckenstein, 1972;Weidmann, 1974;Trautwein, McDonald & Tripathi, 1975;McAllister, Noble & Tsien, 1975;Beeler & Reuter, 1977). Cardiac muscle, like these arteries (Keatinge, 1968a, b), has a largely Na based fast inward current which can produce spike discharges.…”