Calcium homeostasis and sensitization in pulmonary arterial smooth muscle

Abstract

The pulmonary circulation is a low-pressure, low-resistance vascular bed with little to no resting tone under normal conditions. An increase in the [Ca(2+) ]i in PASMCs is an important determinant of contraction, migration, and proliferation. Both Ca(2+) influx through plasma membrane Ca(2+) channels and Ca(2+) release from the SR contribute to a rise in [Ca(2+) ]i . Additionally important in the pulmonary circulation are several kinase-mediated signaling pathways that act to increase the sensitivity of the contractile apparatus to [Ca(2+) ]i . Similarly, cytoskeletal processes resulting in dynamic remodeling of the actin cytoskeleton can further contribute to contractility in the pulmonary circulation. In addition to endocrine, paracrine, and autocrine factors, alveolar hypoxia is an important stimulus for pulmonary vasoconstriction. However, prolonged hypoxia is a critical pathological stimulus associated with the development of pulmonary hypertension and cor pulmonale. In this review, we will discuss recent advances in our understanding of how Ca(2+) homeostasis and sensitization regulate PASMC contractility under both physiological and pathophysiological conditions.

Keywords: actin polymerization; calcium entry; calcium sensitization; hypoxia; pulmonary hypertension; vascular smooth muscle.