AI Article Synopsis
- UK-68,798 significantly prolonged the duration and effective refractory period of cardiac action potentials in canine ventricular muscle and Purkinje fibers, demonstrating its class III antiarrhythmic properties without affecting resting membrane potential or maximum upstroke velocity.
- At concentrations of 5 nM to 1 microM, UK-68,798 increased the effective refractory period in guinea pig papillary muscles without altering conduction velocity, further confirming its lack of class I antiarrhythmic activity.
- In isolated guinea pig ventricular myocytes, UK-68,798 blocked a time-dependent K+ current while not affecting other currents, highlighting its selectivity as a K+ channel blocker, making it a promising candidate for treating dangerous cardiac arr
Article Abstract
UK-68,798 increased the duration and effective refractory period of cardiac action potentials recorded in vitro from canine ventricular muscle and Purkinje fibers in a concentration dependent manner from 5 nM to 1 microM. The resting membrane potential, amplitude and maximum upstroke velocity of action potentials were unaffected by UK-68,798, indicating the selective class III antiarrhythmic properties of this agent. UK-68,798 (5 nM-1 microM) increased the effective refractory period of isolated guinea pig papillary muscles at stimulation frequencies of 1 Hz and 5 Hz without influencing the conduction velocity, further confirming that UK-68,798 is devoid of class I antiarrhythmic activity including block of the sodium channel. Studies using single voltage clamped guinea pig ventricular myocytes indicated that UK-68,798 at concentrations of 50 nM and 2 microM blocks a time-dependent K+ current, with no appreciable effects on the time-independent K+ current or the inward calcium current. UK-68,798 is therefore a highly selective K+ channel blocking agent with class III antiarrhythmic properties, a profile that holds considerable promise for the therapy of life-threatening cardiac arrhythmias.
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