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

Ca²⁺ 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⁺].