Physiological properties and functions of Ca(2+) sparks in rat intrapulmonary arterial smooth muscle cells.
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 Ca(2+) sparks in rat intralobar PASMCs and characterized their spatiotemporal properties and physiological functions. Ca(2+) 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 Ca(2+) channels. Enhanced Ca(2+) influx by BAY K8644, K(+), or high Ca(2+) caused a significant increase in spark frequency. Functionally, enhancing Ca(2+) 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 Ca(2+) concentration ([Ca(2+)]), but only endothelin-1 increased spark frequency. These results suggest that Ca(2+) sparks of PASMCs are similar to those of SASMCs, originate from ryanodine receptors, and are enhanced by Ca(2+) influx. However, they play a different modulatory role on membrane potential and are under agonist-specific regulation independent of global [Ca(2+)].
Division of Pulmonary and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21224, USA.
Carmelle V
CV
Remillard
Wei-Min
WM
Zhang
Larissa A
LA
Shimoda
James S K
JS
Sham
D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000378:metabolism; D004594:Electrophysiology; D019332:Endothelin-1 / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D015220:Calcium Channels; D019332:Endothelin-1; D014662:Vasoconstrictor Agents; D012433:Ryanodine; D002118:Calcium; D009638:Norepinephrine