EFFECTS OF DIMETHYLPROPRANOLOL (UM-272) ON THE ELECTROPHYSIOLOGICAL PROPERTIES OF GUINEA-PIG VENTRICULAR MUSCLES

  • 1 January 1985
    • journal article
    • research article
    • Vol. 234  (2) , 507-514
Abstract
The effects of dimethylpropranolo (UM-272) on transmembrane action potentials were examined in isolated right ventricular papillary muscles of the guinea pig. UM-272 (10-5 to 3 .times. 10-4 M) caused a dose-dependent decrease in the .ovrhdot.Vmax of the action potential. At 3 .times. 10-4 M, a slight decrease in the amplitude of action potential was also observed. The resting potential and the action potential duration were not affected by the drug. In the presence of UM-272 trains of stimuli at rates higher than 0.1 Hz led to an exponential decline in .ovrhdot.Vmax (onset rate, 0.13-0.28/action potential) to a new plateau level. This use-dependent block was augmented at the higher stimulation frequency. The time constant for the recovery of .ovrhdot.Vmax from the use-dependent block (offset) was 7.1-7.3 s. In depolarized papillary muscles with 8 .times. 10-mM [K+]o the inhibitory action of UM-272 on .ovrhdot.Vmax of the 1st action potential after a long quiescent period (tonic block) was augmented markedly, but the rates of onset and offset of the use-dependent block were similar to those in normally polarized preparations under 5 mM [K+]o. The curves relating membrane potential and .ovrhdot.Vmax in preparations stimulated infrequently were shifted by 7.2 mV with UM-272 at 10-4 M in the direction of more negative potentials. UM-272 has kinetically similar use-dependent inhibitory action of the fast Na channels of cardiac muscles as other class Ia antiarrythmic drugs like quinidine or procainamide. This use-dependency and its greater inhibition of .ovrhdot.Vmax in depolarized muscles through the augmentation of tonic block would play a major role for the drug action to prevent ventricular arrhythmias.