Effects of dimethylpropranolol (UM-272) on the electrophysiological properties of guinea-pig ventricular muscles.
The effects of dimethylpropranolol (UM-272) on transmembrane action potentials were examined in isolated right ventricular papillary muscles of the guinea pig. UM-272 (10(-5) to 3 X 10(-4) M) caused a dose-dependent decrease in the Vmax of the action potential. At 3 X 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 Vmax (onset rate, 0.13-0.28 per 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 Vmax from the use-dependent block (offset) was 7.1 to 7.3 sec. In depolarized papillary muscles with 8 or 10 Mm [K+]0, the inhibitory action of UM-272 on Vmax of the first 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+]0. The curves relating membrane potential and 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. These findings suggest that UM-272 has kinetically similar use-dependent inhibitory action of the fast sodium channels of cardiac muscles as other Class Ia antiarrhythmic drugs like quinidine or procainamide.(ABSTRACT TRUNCATED AT 250 WORDS)
I
I
Kodama
N
N
Kondo
S
S
Shibata
K
K
Yamada
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004558:Electric Stimulation; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D011433:Propranolol / Q000031:analogs & derivatives* / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism
D000889:Anti-Arrhythmia Agents; D007473:Ion Channels; C002616:pranolium; D012964:Sodium; D011433:Propranolol