Analysis of the hyperpolarizing effect of catecholamines on canine cardiac Purkinje fibres

Abstract

The hyperpolarization induced by catecholamines on barium‐depolarized (0.2–0.8 mm BaCl) canine cardiac Purkinje fibres, in vitro, was studied by use of conventional microelectrode recordings of transmembrane electrical potentials. Noradrenaline, adrenaline and isoprenaline hyperpolarized Purkinje fibres in a concentration‐dependent manner from a threshold concentration around 5 nm. The three catecholamines were shown to be approximately equipotent. Tachyphylaxis was observed when the interval between catecholamine applications was less than 15 min. Atenolol (10 μm) blocked the hyperpolarization reversibly and theophylline (0.5 mm) potentiated it. Tetrodotoxin (5 μm) did not affect the hyperpolarization induced by isoprenaline. Acetylcholine and histamine, up to 10 μm, were not effective in hyperpolarizing Purkinje fibres. Low extracellular potassium concentrations (zero and 1 mm) did not affect the hyperpolarization, but high extracellular potassium concentrations (10–20 mm), markedly reduced the effect of isoprenaline (100 nm). Reduction of the extracellular sodium concentration produced a roughly proportional reduction in the isoprenaline‐induced hyperpolarization. The hyperpolarization was reversibly blocked in 34 mm sodium Tris‐Tyrode solution. The hyperpolarization was not reduced in Tyrode solution containing 0.6 mm calcium, but was drastically reduced in zero‐calcium Tyrode solution. This effect was reversible. Addition of verapamil (5–10 μm) diminished the hyperpolarization, in a concentration‐dependent manner. This effect was partially reversed after washing. Ouabain (0.7–1 μm) significantly reduced the isoprenaline‐induced hyperpolarization, but 2,4‐dinitrophenol (0.2 mm) did not affect it. Caesium chloride (20 mm) abolished the hyperpolarization. The blockade was only partially reversed upon washing. It is suggested that the hyperpolarization induced by a short exposure to catecholamines is mainly due to an increase in potassium permeability (PK). A mechanism involving calcium‐dependent potassium channels might underlie the increase in PK.

Unaffected electrogenic Na-K pump activity in "diseased" human atrial fibers, as assessed by intracellular K+ activity.

“…Catecholamine stimulates the electrogenic pump in cardiac muscles of bullfrog (AKASU et a!.,1978) and human (IMANISHI and ARITA, 1987), and in rabbit cardiac myocytes (DESILETS and BAUMGARTEN, 1986). There is an alternative explanation that isoproterenol increases the membrane K+ conductance (GADSBY, 1983;NETO and SPERELAKIS, 1989) to increase the Vm. However, it is difficult to explain the increase in 4 by this mechanism.…”

“…3A). The first effect of the drug (depolarization of Vm) seemed to be due to inhibition of electrogenic (outward) Na-K pump current by DUO, while the late effect, i.e., change of Vm in the hyperpolarizing direction, may be due to long-lasting application of DHO, which increased intracellular Na + and Cat + concentrations, both of which secondarily enhanced membrane K + conductance (ISENBERG, 1976;EISNER et al, H. SAKO et al 1984;KAMEYAMA et al, 1984;NETO and SPERELAKIS, 1989). Thus, in Fig.…”

Oral theophylline for treatment of painful left bundle branch block

“…Theophylline, a methylxanthine with adenosine receptor antagonistic action directly antagonizing A1A receptors in both the sinoatrial node and AV node, has a similar chronotropic and dromotropic effect to isoproterenol and is available in both intravenous and oral forms. 11 Although literature is sparse, theophylline has reportedly been suggested for treatment of symptomatic bradycardia in the elderly who declined or could not tolerate pacemaker implantation, bradycardia owing to spinal cord injuries, and, most recently, COVID-19-induced bradycardia. 12 No clear guidelines are available regarding the dosing of theophylline for such an indication; however, current literature suggests that a dose between 200 mg and 700 mg daily is sufficient.…”

Balance of Activity of Sympathetic, Parasympathetic, and Serotoninergic Divisions of the Autonomic Nervous System in Rabbits

“…They can result from activation of adrenoceptors in nervous terminals and cardiomyocytes with modulation of ganglionic excitability [9] and involvement of serotoninergic structures [2,7] in addition to acetylcholine and catecholamines [5,8].…”