Electrophysiological effects of lidocaine, l-chlorpheniramine, and bepridil on rabbit sinus node pacemaker cells

We compared the electrophysiological effects of lidocaine, l-chlorpheniramine, and bepridil on rabbit sinus node pacemaker cells. Only bepridil (0.25-2.0 mg/L) caused a marked reduction in the automaticity of the sinus node. Action potential amplitude, overshoot, and maximum rate of depolarization of phase O (MRD) were all reduced in a dose-dependent manner by bepridil. Decreases in maximum diastolic potential (MDP) and take-off potential were also observed, the former falling to approximately -40 mV when automaticity ceased. On the other hand, lidocaine (12-48 mg/L) depressed the upstroke of the action potential without significantly affecting MDP or take-off potential. The action potential duration was also prolonged at these concentrations. Both MDP and take-off potential were markedly reduced by l-chlorpheniramine (2.9-11.6 mg/L) and these changes were accompanied by reductions in amplitude, overshoot, and MRD of the action potential. A prolongation of the action potential duration was also observed. Pacing the sinus node preparations at a frequency of 4.5 Hz depressed the upstroke of the action potential and led to postoverdrive suppression. l-Chlorpheniramine abolished the postoverdrive suppression, whereas in the presence of lidocaine and bepridil a marked reduction and alternation in action potential amplitude occurred on pacing which made the accurate assessment of sinus node recovery time impossible.