Endothelin-1 and IP3 induced Ca2+ sparks in pulmonary arterial smooth muscle cells.
Endothelin-1 has been implicated as an important modulator or mediator of acute and chronic hypoxic pulmonary hypertension. It has been shown that endothelin-1 increases [Ca2+]i and contraction in pulmonary arterial smooth muscle cells. Recently, we have identified local Ca2+ release transients or Ca2+ sparks, which represent Ca2+ release from clusters of ryanodine receptors on the sarcoplasmic reticulum, in pulmonary arterial smooth muscle cells. These pulmonary Ca2+ sparks were associated with membrane depolarization, and activated specifically by endothelin-1 via endothelin-A receptor activation of phospholipase C and inositol trisphosphate production, possibly through local Ca2+ signaling between inositol trisphosphate receptors and ryanodine receptors. To test this hypothesis, we measured Ca2+ sparks in intralobar pulmonary arterial smooth muscle cells using laser scanning microscopy, and compared the spatiotemporal properties of Ca2+ sparks activated by endothelin-1 and by photorelease of inositol trisphosphate. We found that both endothelin-1 and inositol trisphosphate had similar effects on Ca2+ sparks. They both increased spark frequency, elevated spark amplitude and prolonged duration, without any significant effect on the spatial spread or size of Ca2+ sparks. These results provide further support to the suggestion that inositol trisphosphate production stimulated by endothelin-1 can account for the activation of Ca2+ sparks in pulmonary arterial smooth muscle cells.
Zhang
Wei-Min
WM
Division of Pulmonary and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Lin
Mo-Jun
MJ
Sham
James S K
JS
D000818:Animals; D020013:Calcium Signaling; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D011651:Pulmonary Artery / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D019332:Endothelin-1; D015544:Inositol 1,4,5-Trisphosphate