Modulation of K+ and Ca2+ channels by histamine H1-receptor stimulation in rabbit coronary artery cells

Abstract

1. The modulation of whole-cell K+ and Ca2+ currents by stimulation of histamine H1-receptors in freshly isolated single smooth muscle cells from the rabbit coronary artery was characterized using the patch-clamp technique at 35 degrees C. Single-channel K+ currents were also analysed using the cell-attached patch configuration. 2. The histamine H1-receptor agonist, 2-(2-aminoethyl)pyridine (AEP) (0.1 mM), increased the amplitude of voltage-activated inward Ba2+ currents, recorded using the perforated-patch recording technique, which could be completely blocked by the dihydropyridine antagonist, nicardipine (1 microM). 3. Whole-cell outward K+ currents in rabbit coronary artery cells could be classified into at least two components: (a) a slowly inactivating, 4-aminopyridine (4-AP)-sensitive low-noise current, and (b) a non-inactivating, tetraethylammonium (TEA)-sensitive high-noise current. 4. AEP (0.1 mM) caused changes in whole-cell outward K+ currents which depended upon membrane voltage. Specifically: (a) AEP enhanced the amplitude of outward currents at voltages between -30 and 0 mV, and (b) AEP decreased the outward currents at more positive potentials. 5. The removal of extracellular Ca2+ caused little inhibition of the effects of AEP on K+ currents, whereas the depletion of intracellular Ca2+ stores by pretreatment with ryanodine and caffeine prevented the effects of AEP on K+ channels. Moreover, acute exposure to ryanodine (10 microM) or thapsigargin (1 microM), a Ca(2+)-ATPase inhibitor, caused voltage-dependent changes in the outward currents similar to those observed with AEP. These results suggest that the voltage-dependent effects of AEP on K+ currents are mainly mediated by release of Ca2+ from intracellular stores. 6. The dual stimulatory and inhibitory effect of AEP on whole-cell K+ currents was shown to be due to a differential effect on two distinct types of K+ channels. The stimulatory effect observed over the voltage range -30 to 0 mV was prevented by pretreatment of cells with low concentrations of TEA (1 mM), whereas the inhibitory effect observed at positive potentials was prevented by pretreatment of cells with 4-AP (3 mM). 7. Single-channel recordings revealed two types of unitary K+ currents with conductances of 225 and 70 pS in the cell-attached configuration with symmetrical K+ solutions (150 mM K+ in pipette-150 mM K+ in bath). Bath application of AEP (0.1 mM) caused a marked increase in the open probability of the large conductance channels.(ABSTRACT TRUNCATED AT 400 WORDS)