Modulation of the automaticity by histamine and cimetidine in rabbit sino-atrial node cells

1. Effects of histamine (HIS) and cimetidine (CIM) on the spontaneous action potentials and ionic currents in rabbit sino-atrial node cells were investigated. 2. HIS accelerated the sinus rate at 10 mumol/l, and shortened the action potential duration (APD) at 100 mumol/l, significantly. The positive effects were blocked by CIM (100 mumol/l), but not by diphenhydramine (DPH, 1 mumol/l). HIS (100 mumol/l) elicited a dysrhythmia in 4 out of 10 preparations. Addition of acetylcholine (ACh) (1 mumol/l) depressed the HIS-induced effects, but dysrhythmia occurred in 5 of 10 preparations. 3. CIM (100 mumol/l) caused a negative chronotropic effect. The APD was prolonged, and the Vmax was decreased. Addition of pindolol (0.1 mumol/l) potentiated the depressions. CIM (3 mmol/l) caused a sinus arrest in 3 out of 7 preparations. 4. In voltage-clamp experiments, HIS (100 mumol/l) enhanced the slow inward current (Isi). The delayed rectifying K+ current (IK) and hyperpolarization-activated inward current (Ih) were also increased. The enhancement was inhibited by CIM (100 mumol/l), but not by DPH (1 mumol/l). CIM (100 mumol/l) alone depressed Isi, IK and Ih. Pindolol (0.1 mumol/l) potentiated the CIM-induced depressions significantly. 5. These results suggest that HIS and CIM would modulate the ionic currents mediated through H2-receptors, and that HIS possesses arrhythmogenic action (probably by cAMP accumulation), which is potentiated by ACh.