Ca(2+)-activated Cl- currents in pulmonary arterial myocytes

Abstract

Currents from smooth muscle cells isolated from the pulmonary arterial tree of the rat were recorded under voltage clamp using the whole cell configuration of the patch-clamp technique. Rapid increases in cytosolic free calcium evoked by flash photolysis of Nitr-5 activated a current that, following ion substitution and pharmacological experiments, proved to be carried by Cl-. This current [ICl(Ca)] was evoked independently of photolytic by-products and, although smaller, was still activated in the absence of pipette ATP. Experiments revealed that ICl(Ca) was evoked in 80% in the cells isolated from the main pulmonary artery but only in 43% of the cells isolated from small vessels (200-400 microns ID). Application of caffeine also resulted in activation of ICl(ca), although the response current magnitude was larger in the main pulmonary artery. Photolysis of Nitr-5 still activated ICl(ca) in the presence of caffeine, suggesting that Ca2-release is not a prerequisite for activation of ICl(ca). These results represents in the first electrophysiological recordings of Cl- currents from small pulmonary arterial vessels and indicate that their Ca2+ regulation and/or distribution may be different throughout the pulmonary circulation.

Hypoxic Pulmonary Vasoconstriction

“…In contrast, neither DIDS nor substitution of extracellular Cl Ϫ with I Ϫ induced membrane hyperpolarization in rat proximal PASMC (1090). In addition, photolytic release of intracellular caged Ca 2ϩ induced I Cl(Ca) in 80% of rat proximal PASMC but only 43% of distal PASMC (317). The ability to alter expression of the proteins responsible for I Cl(Ca) and development of more specific pharmacological antagonists should allow the contribution of Cl Ca channels to resting E m in PASMC to be quantified.…”

Relationship between membrane potential, delayed rectifier K+ currents and hypoxia in rat pulmonary arterial myocytes

“…This is particularly important since these vessels possess different electrophysiological (Neylon, Avdonin, Dilley, Larson, Tkachuk & Bobik, 1994;Albarwani et al 1995;Archer, Huang, Reeve, Hampl, Tolarova, Michelakis & Weir, 1996), physiological (Leach et al 1992) and morphological (Sasaki, Kobayashi, Dambara, Kira & Sakai, 1995;Archer et al 1996) properties from those of the large vessels. This problem is compounded further by the observation that pulmonary arterial smooth muscle may also contain two distinct populations of cells (Frid, Moiseeva & Stenmark, 1994;Albarwani et al 1995;Clapp et al 1996).…”

Heterogeneity in 5-HT-Induced Contractile and Proliferative Responses in Rat Pulmonary Arterial Bed

“…The distribution of ion channels (calcium, potassium, calcium-activated chloride channels and stretch-activated nonselective cation channel) [1,2,3,4] as well as mediators activity and expression of their receptor subtypes [endothelin-1, noradrenaline, prostaglandin F2α, 5-hydroxytryptamine (5-HT), nucleotides] [5,6,7,8] vary according to size and/or location of the pulmonary arteries (PA).…”