Block of the transient inward current by R56865 in guinea-pig ventricular myocytes.
Single myocytes isolated from the guinea-pig ventricle were used under voltage-clamp conditions to study the activity of a newly developed drug, R56865, a benzothiazolamine derivative, against digitalis toxicity. Multicellular Purkinje preparations were used in some experiments. The drug blocked the transient inward current (TI) with an apparent KD of 7.5 X 10(-8) M. The blockade was not due to a direct effect on the Na+, Ca2+ exchange current or on the non-selective cation current, the two components of TI. Blockade of TI was accompanied in time with inhibition of after-contractions, which suggests that the drug has an effect on Ca(2+)i transients. At concentrations effective on TI the drug did not block Ca2+ currents or Na+ currents; however the Na+ current was inhibited after the cells had been pretreated with DPI 201-106. It is suggested that the inhibitory effect on TI may be due to an effect on the release of Ca2+ from the sarcoplasmic reticulum or to a reduction in Ca2+ overload via blockade of the Na+ channel.
Leyssens
A
A
Laboratory of Physiology, University of Leuven, Belgium.
Carmeliet
E
E
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D052160:Benzothiazoles; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D006224:Cricetinae; D004070:Digitalis; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006352:Heart Ventricles / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D009206:Myocardium / Q000166:cytology; D010880:Piperidines / Q000494:pharmacology*; D010946:Plants, Medicinal; D010947:Plants, Toxic; D011817:Rabbits; D012964:Sodium / Q000378:metabolism / Q000502:physiology; D013844:Thiazoles / Q000494:pharmacology*
D052160:Benzothiazoles; D010880:Piperidines; D013844:Thiazoles; C054551:R 56865; D012964:Sodium; D002118:Calcium