Introduction

Hypoxic pulmonary vasoconstriction (HPV) is an important regulatory mechanism for diverting pulmonary blood flow from poorly ventilated to well-ventilated lung regions to improve ventilation-perfusion matching and to optimize gaseous exchange. A huge body of literature indicates that this is a multifactorial process with an endpoint increase in cytosolic [Ca2+] ([Ca2+]j) and vasoconstriction in pulmonary arteries. Attention has been focused on the global elevation of [Ca2+]|because it is responsible for the activation of Ca27calmodulin dependent myosin light chain kinase to initiate actin-myosin interactions and smooth muscle contraction. However, the global increase of[Ca2+]j in vascular tissues is mediated by multiple Ca2+ influx pathways, including L-type Ca2+ channels, receptor-operated and store-operated Ca2+ channels, Na+/Ca2+ exchangers, and two types of Ca2+ release channels on the sarcoplasmic reticulum (SR) membrane, the IP3 receptors (IP3Rs) and ryanodine receptors (RyRs). Because of the spatial distributions of these Ca2+transporters, diffusion kinetics of Ca2+ ions and subcellular micro-architecture, local heterogeneity in [Ca2+]j is expected. Theoretical modeling has estimated that, in the vicinity of an open Ca2+conducting channel (Ca2+microdomain), local [Ca2+] can easily exceed 100 |iM (47). Such large local gradients of [Ca2+] can provide fast and specific Ca2+ signals to neighboring effector molecules to trigger Ca2+ dependent processes that may not be responsive to global submicromolar increase in [Ca2+]i; yet which may modulate vascular reactivity.

Local Ca2+ events were first visualized as spontaneous local Ca2+ release transients, or "Ca2+ sparks", in cardiac myocytes by the use of laser scanning confocal microscopy (9). They originate from clusters of RyRs, which are functionally-coupled with L-type Ca2+ channels to form Ca2+release units within the diadic junctions (43), and are considered to be the elementary Ca2+ release events underlying excitation-contraction coupling in cardiac and skeletal muscles. During an action potential, thousands of Ca2+sparks are evoked via the "Ca2+-induced-Ca2+ release" mechanism to generate global Ca2+ transients for muscle contraction. Ca2+ sparks have been identified in various types of vascular and non-vascular smooth muscle cells (SMCs). Recently, we have also identified and characterized Ca2+ sparks in rat intralobar pulmonary arterial SMCs (PASMCs) (39). Emerging evidence suggests thatCa2+ sparks ofPASMCs may regulate pulmonary vascular reactivity in a unique tissue specific manner (24, 37, 39, 50). In this chapter, we will provide a brief review on Ca2+sparks in systemic vascular smooth muscle (20), describe and contrast the properties of Ca2+ sparks ofPASMCs, and discuss possible physiological roles of Ca2+sparks in HPV. We hope this will arouse interest for future investigations on the role of local Ca2+ signaling in HPV.

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