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Capacitative calcium entry as a pulmonary specific vasoconstrictor mechanism in small muscular arteries of the rat
Author(s) -
Snetkov Vladimir A,
Aaronson Philip I,
Ward Jeremy P T,
Knock Gregory A,
Robertson Tom P
Publication year - 2003
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705408
Subject(s) - thapsigargin , contraction (grammar) , chemistry , medicine , mesenteric arteries , endocrinology , calcium , biophysics , artery , biology
The effect of induction of capacitative Ca 2+ entry (CCE) upon tone in small (i.d. 200–500 μm) intrapulmonary (IPA), mesenteric (MA), renal (RA), femoral (FA), and coronary arteries (CA) of the rat was examined. Following incubation of IPA with 100 n M thapsigargin (Thg) in Ca 2+ ‐free physiological salt solution (PSS), a sustained contraction was observed upon reintroduction of 1.8 m M Ca 2+ , which was unaffected by either diltiazem (10 μ M ) or the reverse mode Na + /Ca 2+ antiport inhibitor KB‐R7943 (10 μ M ). An identical protocol failed to elicit contraction in MA, RA, or CA, while a small transient contraction was sometimes observed in FA. The effect of this protocol on the intracellular Ca 2+ concentration ([Ca 2+ ] i ) was assessed using Fura PE3‐loaded IPA, MA, and FA. Reintroduction of Ca 2+ into the bath solution following Thg treatment in Ca 2+ ‐free PSS caused a large, rapid, and sustained increase in [Ca 2+ ] i in all the three types of artery. 100 n M Thg induced a slowly developing noisy inward current in smooth muscle cells (SMC) isolated from IPA, which was due to an increase in the activity of single channels with a conductance of ∼30 pS. The current had a reversal potential near 0 mV in normal PSS, and persisted when Ca 2+ ‐dependent K + and Cl − currents were blocked; it was greatly inhibited by 1 μ M La 3+ , 1 μ M Gd 3+ , and the IP 3 receptor antagonist 2‐APB (75 μ M) , and by replacement of extracellular cations by NMDG + . In conclusion, depletion of intracellular Ca 2+ stores with Thg caused capacitative Ca 2+ entry in rat small muscular IPA, MA, and FA. However, a corresponding contraction was observed only in IPA. CCE in IPA was associated with the development of a small La 3+ ‐ and Gd 3+ ‐sensitive current, and an increased Mn 2+ quench of Fura PE‐3 fluorescence. These results suggest that although CCE occurs in a number of types of small arteries, its coupling to contraction appears to be of particular importance in pulmonary arteries.British Journal of Pharmacology (2003) 140 , 97–106. doi: 10.1038/sj.bjp.0705408