Mechanical and electrical manifestations of the papillary muscles of verapamil-treated adult guinea-pigs under steady state conditions and after a pause.

Abstract

The authors studied the effect of verapamil in 10(-7) to 10(-4) mol.l-1 concentration on the duration of action potentials (AP) and the corresponding isometric contractions (MG) from the right ventricular papillary muscles of adult guinea-pigs. In the steady state, using stimulation frequencies of 0.1, 1 and 2 Hz, verapamil caused dose- and use-dependent shortening of the AP plateau phase (D0) in 10(-5) and 10(-4) mol.l-1 concentration; lower concentrations did not affect the D0. With all the given concentrations, the MG fell in relation to the dose and the stimulation frequency. The pause regimen was defined by the induction of a steady state at 1 Hz frequency, followed by the interpolation of a pause lasting 5 s to 600 s and its effect was studied on the first and second AP after the pause and on the corresponding MG, without any pharmacological treatment and in the presence of verapamil (10(-5) mol.l-1). In the absence of the drug, slight lengthening of the D0 and weakening of the MG, proportional to the length of the pause, occurred after the pause. In the presence of verapamil, the first post-rest contraction after a 10 s pause attained five-fold the value in the steady state, while the second post-rest contraction was much weaker than the first. The possibility that verapamil acts on intracellular links in calcium metabolism, and of disproportion of its effect on the D0 and on contractility when it is administered in low concentrations, is discussed. The most likely mechanism of this effect is the presence of a negative feedback between calcium release from the sarcoplasmic reticulum and membrane electrogenesis.