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Ca2+‐Dependent Cl‐ Channel Activation by Store‐Operated Ca2+ Influx in Rabbit Pulmonary Artery Myocytes
Author(s) -
Angermann Jeff Erik,
Greenwood Iain A,
Leblanc Normand
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1350-a
Subject(s) - cyclopiazonic acid , thapsigargin , chemistry , biophysics , intracellular , myocyte , membrane potential , patch clamp , voltage dependent calcium channel , agonist , medicine , calcium , endocrinology , electrophysiology , receptor , biology , biochemistry
Numerous studies have shown that the Ca 2+ activated Cl − current in vascular smooth muscle (I Cl(Ca) ) can be triggered by various sources of Ca 2+ which include Ca 2+ entry via either voltage‐gated Ca 2+ channels or reverse‐mode Na + / Ca 2+ exchange and spontaneous or agonist‐induced Ca 2+ release from internal stores. We sought to explore the possibility that Ca 2+ entry via store‐operated non‐selective cation channels (SOCs) can elicit I Cl(Ca) in voltage clamped rabbit pulmonary arterial myocytes. Thapsigargin (THG) or cyclopiazonic acid (CPA) elicited a current reversing near 0 mV during an initial hyperpolarizing (HP) step, and an outward time‐dependent I Cl(Ca) at +90 mV followed by an I Cl(Ca) tail at 80 mV. The magnitude of both outward and tail currents increased exponentially with membrane HP. Measuring intracellular calcium with Fluo4, CPA led to an initial Ca 2+ transient followed by a sustained elevation of [Ca 2+ ] i likely supported by Ca 2+ entry through SOCs. During sustained phase Ca 2+ elevation, application of K ATP agonist levcromakalim (LEV) further increased [Ca 2+ ] i . These results indicate that graded driving force‐dependent Ca 2+ entry via I SOC during HP steps or following exposure to LEV may activate I Cl(Ca) , and suggest a relationship between two important mechanisms regulating membrane potential and pulmonary arterial tone. [NHLBI: 1 RO1 HL075477‐01‐A2 (NL); COBRE: NCRR 5 P20 RR15581 (NL)]