Abstract

The electrophysiological effects of endothelin (ET)-1 were compared in myocytes isolated from rat small pulmonary artery, basilar artery and aorta. ET-1 evoked depolarization in all three smooth muscle cell types. Depolarizing oscillations in membrane current also were observed in pulmonary and aortic myocytes. In voltage-clamp experiments ET-1 induced a gradual inhibition of the Ca⁺⁺-independent outward current (I_K) in pulmonary and aortic myocytes, whereas in basilar myocytes ET-1 inhibited the Ca⁺⁺-activated K⁺ current (I_K(Ca)). ET-1 also evoked a transient enhancement of I_K(Ca) and oscillations in inward current in aortic and pulmonary myocytes. The inward currents were inhibited by caffeine, which suggests Ca⁺⁺-dependent activation. Ion-exchange experiments indicated that in pulmonary myocytes oscillatory currents were caused solely by the movement of Cl⁻, whereas in aortic myocytes they were the consequence of both Ca⁺⁺-activated Cl⁻ (I_Cl(Ca)) and nonselective cation currents (I_NS). No inward current was evoked in basilar myocytes in response to ET-1 or photorelease of Ca⁺⁺, which suggests that these cells do not possess I_Cl(Ca). Experiments with ET receptor ligands indicated that in basilar myocytes ET_Areceptor stimulation is responsible for I_K(Ca) inhibition, whereas in aortic and pulmonary myocytes ET_B and ET_A receptor stimulation mediates inhibition of I_K and activation of I_Cl(Ca), I_NSand I_K(Ca), respectively. In the future, it may be possible to exploit these differential effects of ET-1 pharmacologically to assist development of tissue-specific modulators for the treatment of vascular disease.