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Characterization of receptor‐ and store‐operated cation currents in rat pulmonary arterial smooth muscle cells (PASMCs)
Author(s) -
Lin MoJun,
Yang XiaoRu,
Sham James S.K.
Publication year - 2008
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.22.1_supplement.1150.12
Subject(s) - agonist , chemistry , nifedipine , cyclopiazonic acid , hypoxic pulmonary vasoconstriction , extracellular , medicine , pulmonary hypertension , endocrinology , receptor , biophysics , intracellular , biology , biochemistry , calcium
Store‐ and receptor‐operated cation channels (SOC and ROC) in PASMCs have been implicated to play important roles in many physiological functions, including hypoxia‐ and agonist‐induced vasoconstriction, and pulmonary hypertension. Here we characterized the SOC and ROC currents in rat intralobar PASMCs. PASMCs were whole‐cell voltage‐clamped. K + and Ca 2+ currents were eliminated by substituting K + with Cs + , and by nifedipine. Depletion of SR Ca 2+ stores with cyclopiazonic acid activated a small inward current at −60 mV. The current was elicited with a time‐delay, exhibited typical bimodal dependence to extracellular Ca 2+ due to the effect of anomalous mole fraction, and was blocked by La 3+ or substitution of Na + with N‐methyl‐D‐glucamine. I‐V relationship of La 3+ ‐sensitive SOC current was quasi‐linear with a reverse potential close to 0 mM, indicative of its non‐selective nature. ROC agonist 1‐oleoyl‐2‐acetyl‐sn‐glycerol also activated a La 3+ (1 mM) sensitive non‐selective cation current with slight outward rectification. Moreover, ROC currents recorded in PASMCs of chronic hypoxic rats (10% O 2 , 4 weeks) were significantly larger than those of normoxic rats. These results are consistent with the notion that functional SOC and ROC are present in PASMCs and their activities are up‐regulated in hypoxic pulmonary hypertension. (Supported by NIH R01HL074134, NSFC 30670772 and NSF(Fujian) C0620002)