Effects of histamine and endothelin-1 on membrane potentials and ion currents in bovine tracheal smooth-muscle cells

We tested the effects of tetraethylammonium (TEA), acetylcholine (ACh), his tamine, and endothelin-l on single airway smooth-muscle cells from bovine t rachea, using the patch-clamp technique. Resting membrane potential was -48 +/- 1 mV (n = 47). Both TEA and ACh significantly depolarized the membrane , by +28 +/- 4 mV (P < 0.001, n = 12) and +21 +/- 2 mV (P < 0.01, n = 7), r espectively, in the whole-cell configuration. In contrast, both histamine a nd endothelin-1 hyperpolarized the membrane, by -21 +/- 6 mV (P < 0.01, n = 8) and -15 +/- 2 mV (P < 0.01, n = 8), respectively. Calcium-dependent lar ge-conductance K+-channels (127 pS) and small-conductance K+ channels (21 p S) were identified in excised patches. The small-conductance K+ channel was inhibited by 4-aminopyridine and activated by both histamine and endotheli n-1. Furthermore, TEA did not alter the membrane hyperpolarization by these agonists, suggesting that the small-conductance K+ channel or delayed-rect ifier K+ channel was involved in the membrane hyperpolarization. Membrane h yperpolarization by histamine and endothelin-1 suggests that activation of voltage-dependent calcium channels (VDCCs) or of calcium influx does not co ntribute substantially to the contractile response of airway smooth-muscle contraction to these agonists.