Abstract
Although endothelin (ET)-1 is an important regulator of pulmonary vascular tone, little is known about the mechanisms by which ET-1 causes contraction in this tissue. Using the whole cell patch-clamp technique in rat intrapulmonary arterial smooth muscle cells, we found that ET-1 and the voltage-dependent K+ (K(V))-channel antagonist 4-aminopyridine, but not the Ca2+-activated K+-channel antagonist charybdotoxin (ChTX), caused membrane depolarization. In the presence of 100 nM ChTX, ET-1 (10-10 to 10-7 M) caused a concentration-dependent inhibition of K+ current (56.2 ± 3.8% at 10-7 M) and increased the rate of current inactivation. These effects of ET-1 on K+ current were markedly reduced by inhibitors of protein kinase C (staurosporine and GF 109203X) and phospholipase C (U-73122) or under Ca2+- free conditions and were mimicked by activators of protein kinase C (phorbol 12-myristate 13-actetate and 1,2-dioctanoyl-sn-glycerol). These data suggest that ET-1 modulated pulmonary vascular reactivity by depolarizing pulmonary arterial smooth muscle, due in part to the inhibition of K(V) current that occurred via activation of the phospholipase C-protein kinase C signal transduction pathway.
Original language | English (US) |
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Pages (from-to) | L842-L853 |
Journal | American Journal of Physiology - Lung Cellular and Molecular Physiology |
Volume | 274 |
Issue number | 5 18-5 |
DOIs | |
State | Published - May 1998 |
Keywords
- Membrane potential
- Patch clamp
- Potassium ion
- Protein kinase C
ASJC Scopus subject areas
- Physiology
- Pulmonary and Respiratory Medicine
- Physiology (medical)
- Cell Biology