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This review describes the ionic heterogeneity manifest in the pulmonary circulation, particularly as it pertains to hypoxic pulmonary vasoconstriction (HPV) and pulmonary arterial hypertension (PAH). Heterogeneity in potassium (K⁺) channels, key regulators of vascular tone, cell proliferation, and apoptosis rates, contribute to the diverse response of vascular segments to hypoxia and to the localization of pathological changes in PAH. Pulmonary artery (PA) and pulmonary vein (PV) smooth muscle cells (SMC) express several K⁺ channel families, including calcium-sensitive (KCa), voltage-gated (K_v), inward rectifier (Kir), and 2-pore channels. Diversity is created by heterogeneous occurrence of alternatively spliced, mRNA species, assembly of heterotetrameric channels from diverse α-subunits, and association of channels with regulatory β-subunits. Local heterogeneity in transcription factor activity may underlie …