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

Abstract

SUMMARY1. We studied the effects of a toxic concentration of ouabain on transmembrane electrical activity and on mechanical behaviour of right ventricular papillary muscles from ferrets in a single sucrose-gap using current clamp and voltage clamp.2. Ouabain (14-1-8 /M) induced oscillatory after-potentials and after-concentrations in current-clamp experiments. Voltage clamp showed that the oscillatory after-potential was caused by a transient inward current, similar to that in Purkinje fibres.3. The transient current had a sigmoidal dependence on the preceding (activating) voltage step VI, with a threshold around -13 mV and a plateau between + 10 and 20 mV. There was a decline in current amplitude for more positive clamps. When activated by a fixed VI voltage step, and measured at different repolarization levels V2, the transient current manifested an inverse dependence on V2 between -50 and -10 mV. No outward transient current could be detected. Total replacement of Na in the bathing medium by Tris or by sucrose abolished the transient current.4. Ouabain caused an increase of phasic (twitch) tension responses to voltage steps at all potentials without shifting the curve relating these variables on the voltage axis. The drug evoked an even greater increase in the tonic tension responses.5. After prolonged exposure, oscillatory mechanical responses were frequently recorded during positive voltage steps. Unlike the after-contraction, these mechanical fluctuations were not consistently damped and were not accompanied by detectable synchronous current fluctuations. Catecholamines and dibutyryl cyclic AMP markedly reduced the amplitude of the tonic contraction and the mechanical oscillations but increased their frequency. Caffeine had no effect on the tonic contraction amplitude but abolished the fluctuations.6. These results support the proposal that Ca is transiently released from the overloaded sarcoplasmic reticulum in ouabain-intoxicated muscle and may evoke oscillatory responses in nearby contractile fibrils. When these transient increases of sarcoplasmic free Ca are large enough, they may induce the transient transmembrane current described above.

Ionic mechanisms of transient inward current in the absence of Na(+)‐Ca2+ exchange in rabbit cardiac Purkinje fibres.

“…under our experimental conditions, Na+-Ca2+ exchange cannot be the charge carrier of this current. This current is similar to the transient inward current described previously (Lederer & Tsien, 1976;Kass et al 1978 a, b;Eisner & Lederer, 1979a, b;Karagueuzian & Katzung, 1982;Noble, 1984;Arlock & Katzung, 1985;Cannell & Lederer, 1986;Noble, 1986;Brown et al 1986;Fedida et al 1987 a;Lipp & Pott, 1988;Han & Ferrier, 1991) in that it is generated by repolarization from a previous depolarizing pulse, followed a similar time course, and occurred in response to Ca2+ overload. In the following discussion we will therefore refer to this current as TI.…”

“…Recent studies at the single-channel level indicate that mammalian myocardium contains a calcium-activated cationic channel that is selective for monovalent ions (Ehara, Noma & Ono, 1988;Hill, Coronado & Strauss, 1988). On the other hand, Na+-Ca2+ exchange (Eisner & Lederer, 1985;Kimura, Miyamae & Noma, 1987), which plays an essential role in calcium extrusion following 20 MECHANISMS OF TI IN Nat-FREE SOLUTION each contraction (Chapman, 1983;Bridge, Smolley & Spitzer, 1990), could also generate TI when the intracellular Ca2+ is significantly elevated (Karagueuzian & Katzung, 1982;Noble, 1984;Arlock & Katzung, 1985;Brown, Noble, Noble & Taupignon, 1986;Fedida, Noble, Rankin & Spindler, 1987 a;Fedida, Noble, Shimoni & Spindler, 1987 b;Lipp & Pott, 1988;Egan, Noble, Noble, Powell, Spindler & Twist, 1989). In general, experimental evidence favouring the cationic channel has come from experiments on Purkinje fibres, whereas observations made in muscle and sinus node cells suggest Na+-Ca2+ exchange as the primary mechanism (January & Fozzard, 1988;Ferrier, 1991); however, both mechanisms might be operative in either tissue (Ehara et al 1988;Giles & Shimoni, 1989a, b;Han & Ferrier, 1990).…”

Mechanisms of arrhythmogenic delayed and early afterdepolarizations in ferret ventricular muscle.

“…Nevertheless, considerable uncertainty still surrounds the exact role of Ca2+. The link between sarcolemmal Ca2+ entry pathways and the DAD remains unclear, with controversy as to whether sarcolemmal Ca2+ entry (4) or intracellular Ca2+ release (5,6) is of primary importance.…”

Responses of cutaneous mechanoreceptors within fingerpad to stimulus information for tactile softness sensation of materials

“…It was reported that the maximum compressive or tensile component of stresses dominated the responses of SAI's cutaneous mechanoreceptors. While the relationship between stresses and receptor current was unknown, mechanical sensory cells such as hair cells and pain receptors exhibited sigmoidal stimulus-current curves (Holt and Corey 2000;Siemens et al 2006), and the same trend of tension-Voltage for muscles existed (Karagueuzian and Katzung 1982). For this reason, the transduction of SAI mechanoreceptors in this work was described as a sigmoidal function by…”