Physiological properties and functions of Ca2+sparks in rat intrapulmonary arterial smooth muscle cells

2002 ◽  
Vol 283 (2) ◽  
pp. L433-L444 ◽  
Author(s):  
Carmelle V. Remillard ◽  
Wei-Min Zhang ◽  
Larissa A. Shimoda ◽  
James S. K. Sham
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Smooth Muscle Cells ◽  
Ryanodine Receptors ◽  
Muscle Cells ◽  
Feedback Mechanism ◽  
Arterial Smooth Muscle ◽  
Endothelin 1 ◽  
Arterial Smooth Muscle Cells ◽  
Specific Regulation

Ca+spark has been implicated as a pivotal feedback mechanism for regulating membrane potential and vasomotor tone in systemic arterial smooth muscle cells (SASMCs), but little is known about its properties in pulmonary arterial smooth muscle cells (PASMCs). Using confocal microscopy, we identified spontaneous Ca2+ sparks in rat intralobar PASMCs and characterized their spatiotemporal properties and physiological functions. Ca2+ sparks of PASMCs had a lower frequency and smaller amplitude than cardiac sparks. They were abolished by inhibition of ryanodine receptors but not by inhibition of inositol trisphosphate receptors and L-type Ca2+ channels. Enhanced Ca2+ influx by BAY K8644, K+, or high Ca2+ caused a significant increase in spark frequency. Functionally, enhancing Ca2+ sparks with caffeine (0.5 mM) caused membrane depolarization in PASMCs, in contrast to hyperpolarization in SASMCs. Norepinephrine and endothelin-1 both caused global elevations in cytosolic Ca2+ concentration ([Ca2+]), but only endothelin-1 increased spark frequency. These results suggest that Ca2+ sparks of PASMCs are similar to those of SASMCs, originate from ryanodine receptors, and are enhanced by Ca2+ influx. However, they play a different modulatory role on membrane potential and are under agonist-specific regulation independent of global [Ca2+].

Mobilization of intracellular Ca2+ by endothelin-1 in rat intrapulmonary arterial smooth muscle cells

2000 ◽  
Vol 278 (1) ◽  
pp. L157-L164 ◽  
Author(s):  
Larissa A. Shimoda ◽  
J. T. Sylvester ◽  
James S. K. Sham
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Arterial Smooth Muscle ◽  
Voltage Gated ◽  
Endothelin 1 ◽  
Intracellular Release ◽  
Intracellular Ca ◽  
Pulmonary Arterial ◽  
Arterial Smooth Muscle Cells

Endothelin-1 (ET-1) increases intracellular Ca2+ concentration ([Ca2+]i) in pulmonary arterial smooth muscle cells (PASMCs); however, the mechanisms for Ca2+ mobilization are not clear. We determined the contributions of extracellular influx and intracellular release to the ET-1-induced Ca2+ response using Indo 1 fluorescence and electrophysiological techniques. Application of ET-1 (10−10 to 10−8 M) to transiently (24–48 h) cultured rat PASMCs caused concentration-dependent increases in [Ca2+]i. At 10−8 M, ET-1 caused a large, transient increase in [Ca2+]i (>1 μM) followed by a sustained elevation in [Ca2+]i(<200 nM). The ET-1-induced increase in [Ca2+]i was attenuated (<80%) by extracellular Ca2+ removal; by verapamil, a voltage-gated Ca2+-channel antagonist; and by ryanodine, an inhibitor of Ca2+ release from caffeine-sensitive stores. Depleting intracellular stores with thapsigargin abolished the peak in [Ca2+]i, but the sustained phase was unaffected. Simultaneously measuring membrane potential and [Ca2+]i indicated that depolarization preceded the rise in [Ca2+]i. These results suggest that ET-1 initiates depolarization in PASMCs, leading to Ca2+influx through voltage-gated Ca2+ channels and Ca2+ release from ryanodine- and inositol 1,4,5-trisphosphate-sensitive stores.

Phosphatidylinositol 3,5-bisphosphate increases intracellular free Ca2+ in arterial smooth muscle cells and elicits vasocontraction

2011 ◽  
Vol 300 (6) ◽  
pp. H2016-H2026 ◽  
Author(s):  
Neerupma Silswal ◽  
Nikhil K. Parelkar ◽  
Michael J. Wacker ◽  
Marco Brotto ◽  
Jon Andresen
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Ryanodine Receptors ◽  
Muscle Cells ◽  
Arterial Smooth Muscle ◽  
Aortic Smooth Muscle Cells ◽  
Aortic Smooth Muscle ◽  
Voltage Dependent ◽  
Intracellular Ca ◽  
Arterial Smooth Muscle Cells

Phosphoinositide (3,5)-bisphosphate [PI(3,5)P2] is a newly identified phosphoinositide that modulates intracellular Ca2+ by activating ryanodine receptors (RyRs). Since the contractile state of arterial smooth muscle depends on the concentration of intracellular Ca2+, we hypothesized that by mobilizing sarcoplasmic reticulum (SR) Ca2+ stores PI(3,5)P2 would increase intracellular Ca2+ in arterial smooth muscle cells and cause vasocontraction. Using immunohistochemistry, we found that PI(3,5)P2 was present in the mouse aorta and that exogenously applied PI(3,5)P2 readily entered aortic smooth muscle cells. In isolated aortic smooth muscle cells, exogenous PI(3,5)P2 elevated intracellular Ca2+, and it also contracted aortic rings. Both the rise in intracellular Ca2+ and the contraction caused by PI(3,5)P2 were prevented by antagonizing RyRs, while the majority of the PI(3,5)P2 response was intact after blockade of inositol (1,4,5)-trisphosphate receptors. Depletion of SR Ca2+ stores with thapsigargin or caffeine and/or ryanodine blunted the Ca2+ response and greatly attenuated the contraction elicited by PI(3,5)P2. The removal of extracellular Ca2+ or addition of verapamil to inhibit voltage-dependent Ca2+ channels reduced but did not eliminate the Ca2+ or contractile responses to PI(3,5)P2. We also found that PI(3,5)P2 depolarized aortic smooth muscle cells and that LaCl3 inhibited those aspects of the PI(3,5)P2 response attributable to extracellular Ca2+. Thus, full and sustained aortic contractions to PI(3,5)P2 required the release of SR Ca2+, probably via the activation of RyR, and also extracellular Ca2+ entry via voltage-dependent Ca2+ channels.

Membrane Potential and Calcium Channels in Arterial Smooth Muscle Cells

1989 ◽  
pp. 37-44
Author(s):  
Mark T. Nelson ◽  
Nicholas B. Standen ◽  
Joseph E. Brayden ◽  
Jennings F. Worley
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Calcium Channels ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Arterial Smooth Muscle ◽  
Arterial Smooth Muscle Cells
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