title: Inhibition of potassium outward currents and pacemaker current in sheep cardiac Purkinje fibres by the verapamil derivative YS 035.
abstract: The electrophysiologic mode of action and potency of the verapamil derivative YS 035 (N,N-bis-(3,4-dimethoxyphenethyl)-N-methyl amine) were investigated in sheep cardiac Purkinje fibres. Action potential duration measured at a repolarization level of -60 mV (APD-60) and membrane currents recorded with the two-microelectrode voltage-clamp technique were evaluated. At 10 mumols/l YS 035 APD-60 was increased to about 115% of reference. Prolongation measured as percentage of the respective control exhibited on the average no dependence on stimulation frequency (0.17-2 Hz). At 100 mumols/l membrane became depolarized to about -50 mV and action potentials could no longer be elicited. Further study was focussed on effects on outward currents, mostly activated at a frequency of 0.05 Hz. Transient outward current (ito) was completely blocked at 100 mumols/l and half-maximal inhibition occurred at about 14 mumols/l. Inwardly rectifying potassium current (ik1) was reduced to 47% of reference at 100 mumols/l. An initially activating outward current at positive membrane potentials (iinst) was reduced to 73% at 100 mumols/l. Time-dependent (delayed) outward current (iK) was on the average not affected up to 100 mumols/l. Besides inhibition of repolarizing outward currents YS 035 completely blocked pacemaker current (if) at 100 mumols/l and half-maximal reduction was achieved at 5 mumols/l. YS 035 (1-100 mumols/l) did not clearly affect time constants of activation at selected test potentials (IK: +35 mV; if: -90 mV) or inactivation (ito: 0 mV). Voltage-dependent control mechanisms of currents (ito, if) were not influenced by YS 035 but the amount of available current was reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Institut für Pharmakologie, Universität Düsseldorf, Federal Republic of Germany.
authors.forename: F
authors.initials: F
authors.lastname: Berger
authors.forename: U
authors.initials: U
authors.lastname: Borchard
authors.forename: D
authors.initials: D
authors.lastname: Hafner
authors.forename: T
authors.initials: T
authors.lastname: Kammer
authors.forename: T
authors.initials: T
authors.lastname: Weis
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D010627:Phenethylamines / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects; D012756:Sheep
chemical_list: D002121:Calcium Channel Blockers; D010627:Phenethylamines; C041094:N,N-bis(3,4-dimethoxyphenethyl)-N-methylamine