Differential electrophysiological actions of endothelin-1 on Cl- and K+ currents in myocytes isolated from aorta, basilar and pulmonary artery.
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 (IK) in pulmonary and aortic myocytes, whereas in basilar myocytes ET-1 inhibited the Ca(++)-activated K+ current (IK(Ca)). ET-1 also evoked a transient enhancement of IK(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-(ICl(Ca)) and non-selective cation currents (INS). 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 ICl(Ca). Experiments with ET receptor ligands indicated that in basilar myocytes ETA receptor stimulation is responsible for IK(Ca) inhibition, whereas in aortic and pulmonary myocytes ETB and ETA receptor stimulation mediates inhibition of IK and activation of ICl(Ca), INS and IK(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.
Salter
K J
KJ
University of Oxford, Department of Pharmacology, United Kingdom.
Kozlowski
R Z
RZ
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001488:Basilar Artery / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D018118:Chloride Channels / Q000187:drug effects*; D019332:Endothelin-1 / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects*; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017466:Receptors, Endothelin / Q000502:physiology
D018118:Chloride Channels; D019332:Endothelin-1; D015221:Potassium Channels; D017466:Receptors, Endothelin; D002118:Calcium