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L‐type Ca2+ channels are expressed but not activated by KCl in rat small mesenteric veins
Author(s) -
Thakali Keshari,
Sonkusare Swapnil,
Stimers Joseph R.,
Rusch Nancy J.
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.912.31
Subject(s) - contraction (grammar) , nifedipine , chemistry , extracellular , biophysics , thapsigargin , l type calcium channel , egta , voltage dependent calcium channel , endocrinology , medicine , anatomy , calcium , biology , biochemistry
Calcium channel blockers (CCBs) reduce afterload but not preload in vivo , suggesting that arteries and veins use different mechanisms to mediate contraction. We investigated this hypothesis using pressurized small mesenteric arteries (MA) and veins (MV) from male Sprague Dawley rats. Both MA and MV contracted robustly to 60 mmol/L KCl. Nifedipine (1 nmol/L – 1 μmol/L) and diltiazem (10 nmol/L – 10 μmol/L) each maximally reversed the KCl‐induced contraction in MA by 93%. Although we detected an abundance of L‐type Ca 2+ channel mRNA and protein by RT‐PCR and Western blot, respectively, MV did not dilate significantly to either CCB. Whole‐cell patch‐clamp studies revealed that Ca 2+ current (I Ca ) density in freshly dissociated smooth muscle cells from MV was 68% less than in cells from MA (MV, −3.8±0.7 pA/pF; MA, −11.7±3.0 pA/pF). However, the I Ca was similarly sensitive to block by 100 nmol/L nifedipine (percent block: MA, 50%; MV, 60%). The KCl‐induced contraction in MA was prevented by removal of extracellular Ca 2+ , whereas 60±7% of the response persisted in MV. This persistent contraction was eliminated by EGTA (0.5 mmol/L) or thapsigargin (1 μmol/L). Thus, MV express functional L‐type Ca 2+ channels, but these channels do not contribute to KCl‐induced contraction. Instead, a unique mechanism linking membrane depolarization to intracellular Ca 2+ release may exist in veins.