Voltage dependence of cardiac delayed rectifier block by methanesulfonamide class III antiarrhythmic agents. Export

@article{citeulike:1387953, abstract = {Voltage-clamp experiments were performed on isolated guinea pig ventricular myocytes to examine the voltage dependence of delayed rectifier block by methanesulfonamide channel blockers. Voltage-dependent channel block, in which block decreases as membrane potential is made more positive, could contribute to the phenomenon of reverse use dependence, in which the magnitude of the drug-induced prolongation in action potential duration (APD) is inversely proportional to stimulation rate. To determine whether such a voltage dependence exists, concentration-response curves were generated for dofetilide, E-4031, sematilide, and D,L-sotalol at test potentials ranging from 0 to 60 mV. All agents blocked current in a manner consistent with selective blockade of the rapidly activating component of delayed rectifier current, IKr. The rank order of potency was E-4031 approximately dofetilide > sematilide > sotalol. Block of tail currents by this class of compounds was more potent after test potentials to +60 mV than after those < or = 0-10 mV. These data are inconsistent with voltage-dependent channel block being a contributing factor to reverse use-dependence and suggest that other mechanisms must be responsible for this phenomenon.}, address = {Sterling Winthrop, Inc., Collegeville, PA 19426-0900.}, author = {Krafte, D. S. and Volberg, W. A.}, citeulike-article-id = {1387953}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/7511733}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=7511733}, issn = {0160-2446}, journal = {J Cardiovasc Pharmacol}, keywords = {block, sotalol}, month = {January}, number = {1}, pages = {37--41}, posted-at = {2007-06-13 18:41:40}, priority = {2}, title = {Voltage dependence of cardiac delayed rectifier block by methanesulfonamide class III antiarrhythmic agents.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/7511733}, volume = {23}, year = {1994} }

TY - JOUR ID - citeulike:1387953 L3 - citeulike-article-id:1387953 N2 - Voltage-clamp experiments were performed on isolated guinea pig ventricular myocytes to examine the voltage dependence of delayed rectifier block by methanesulfonamide channel blockers. Voltage-dependent channel block, in which block decreases as membrane potential is made more positive, could contribute to the phenomenon of reverse use dependence, in which the magnitude of the drug-induced prolongation in action potential duration (APD) is inversely proportional to stimulation rate. To determine whether such a voltage dependence exists, concentration-response curves were generated for dofetilide, E-4031, sematilide, and D,L-sotalol at test potentials ranging from 0 to 60 mV. All agents blocked current in a manner consistent with selective blockade of the rapidly activating component of delayed rectifier current, IKr. The rank order of potency was E-4031 approximately dofetilide > sematilide > sotalol. Block of tail currents by this class of compounds was more potent after test potentials to +60 mV than after those < or = 0-10 mV. These data are inconsistent with voltage-dependent channel block being a contributing factor to reverse use-dependence and suggest that other mechanisms must be responsible for this phenomenon. IS - 1 JF - J Cardiovasc Pharmacol SN - 0160-2446 AD - Sterling Winthrop, Inc., Collegeville, PA 19426-0900. EP - 41 TI - Voltage dependence of cardiac delayed rectifier block by methanesulfonamide class III antiarrhythmic agents. VL - 23 SP - 37 KW - block KW - sotalol AU - Krafte, DS AU - Volberg, WA PY - 1994/01// UR - http://view.ncbi.nlm.nih.gov/pubmed/7511733 ER -