Key roles of Src family tyrosine kinases in the integrity of the pulmonary vascular bed.

T he pulmonary blood vessels have unique structural and functional properties. The pulmonary circulation is a high-flow, low-resistance, low-pressure system, which is mainly explained by two important characteristics of the pulmonary vascular bed: a high compliance of the pulmonary pre-capillary arterioles characterised by thin media and a high capacity to recruit vessels available to cope with an increase in blood flow. Local variations in response to various vasoactive molecules, such as hypoxia and nitric oxide, are well known, but the molecular mechanisms underlying the sensing of those stimuli remain obscure. In contrast to the systemic arteries, the hypoxic stimulus induces vasoconstriction of the pulmonary arteries, an effect that is more pronounced as the vessel diameter decreases [1, 2]. Different potassium channels are expressed and distributed in several types of pulmonary arterial smooth muscle cells (PA-SMCs) and contribute to this large functional diversity. Although voltage-gated potassium channel (KV)1.2, KV1.5, KV2.1, KV3.1b and KV9.3 play important roles in the hypoxia-inhibited potassium current found in PA-SMCs, much attention has been attracted by KV1.5 [3]. In addition to the KV family, calcium-activated (KCa) [4], two-pore domain (K2P) [5] and ATP-sensitive potassium channels [6] have been documented to play crucial roles in setting the resting membrane potential (Em) in PA-SMCs under either basal or hypoxic conditions. TWIK-related acid-sensitive potassium channels (TASK)-1–3 belong to the K2P family. TASK-1 is thought to be a critical element for both homeostasis and pathophysiology. Indeed, TASK-1 channels play a role in the Em and render these excitable cells sensitive to a variety of vasoactive factors. In addition, TASK-1 channels are constitutively active, and are sensitive to extracellular pH in the physiological range and to volatile anaesthetics such as isoflurane. It has been demonstrated that TASK-1 channels are inhibited by hypoxia but the precise mechanisms remain obscure [7, 8].