Revisiting the Large-Conductance Calcium-Activated Potassium (BKCa) Channels in the Pulmonary Circulation

• Published in: Biomolecules (Basel, Switzerland) Vol. 11; no. 11; p. 1629
• Main Authors: Guntur, Divya, Olschewski, Horst, Enyedi, Péter, Csáki, Réka, Olschewski, Andrea, Nagaraj, Chandran
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03.11.2021; MDPI
• Subjects: Alkalosis; Animal models; Animals; Blood vessels; Calcium (intracellular); Calcium channels; Calcium channels (voltage-gated); Calcium conductance; Catecholamines; Channel opening; Endoplasmic reticulum; Fetuses; Humans; Hypertension, Pulmonary - metabolism; Hypoxia; Hypoxia - metabolism; KCNMA1; KCNMB1; KCNMB2; large conductance calcium-activated potassium (BKCa) channels; Large-Conductance Calcium-Activated Potassium Channels - metabolism; LRRC26; Lung - metabolism; Lung diseases; Membrane potential; Neonates; Nervous system; Pathophysiology; Peptides; Potassium; Potassium channels (calcium-gated); Potassium channels (voltage-gated); Potassium conductance; Pulmonary arteries; Pulmonary Circulation; Review; Smooth muscle; Therapeutic targets; Vasoconstriction; Vasodilation; Veins & arteries; Ventilators; LRRC26; hypoxia; pulmonary circulation; KCNMB1; pulmonary hypertension; KCNMA1; KCNMB2; large conductance calcium-activated potassium (BKCa) channels; fetal to neonatal transition
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom11111629

Potassium ion concentrations, controlled by ion pumps and potassium channels, predominantly govern a cell's membrane potential and the tone in the vessels. Calcium-activated potassium channels respond to two different stimuli-changes in voltage and/or changes in intracellular free calcium. Large conductance calcium-activated potassium (BKCa) channels assemble from pore forming and various modulatory and auxiliary subunits. They are of vital significance due to their very high unitary conductance and hence their ability to rapidly cause extreme changes in the membrane potential. The pathophysiology of lung diseases in general and pulmonary hypertension, in particular, show the implication of either decreased expression and partial inactivation of BKCa channel and its subunits or mutations in the genes encoding different subunits of the channel. Signaling molecules, circulating humoral molecules, vasorelaxant agents, etc., have an influence on the open probability of the channel in pulmonary arterial vascular cells. BKCa channel is a possible therapeutic target, aimed to cause vasodilation in constricted or chronically stiffened vessels, as shown in various animal models. This review is a comprehensive collation of studies on BKCa channels in the pulmonary circulation under hypoxia (hypoxic pulmonary vasoconstriction; HPV), lung pathology, and fetal to neonatal transition, emphasising pharmacological interventions as viable therapeutic options.