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Voltage‐dependent calcium channels in human renal arteries
Author(s) -
Hansen Pernille B,
Walter Steen,
Marcussen Niels,
Jensen Boye L,
Skott Ole
Publication year - 2009
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.23.1_supplement.804.22
Subject(s) - mibefradil , myograph , constriction , l type calcium channel , voltage dependent calcium channel , chemistry , nifedipine , medicine , endocrinology , calcium , anatomy , vasodilation
Several types of voltage‐dependent calcium channels (VDCC) Ca v 1.2 (L‐type), Ca v 2.1 (P/Q‐ type) and Ca v 3.1/ Ca v 3.2 (T‐ type) are expressed in vascular smooth muscle cells from rodents and are important for renal resistance. We examined whether human renal arteries express several types of VDCC and assessed their functional importance. The expression of Ca v 1.2, mRNA was demonstrated in all human renal and interlobular arteries tested whereas Ca v 2.1, Ca v 3.1 and Ca v 3.2 only were observed in some patients. Immunolabeling revealed expression of Ca v 1.2 and Ca v 2.1 in human arteries. Using a myograph set‐up, the functional importance of different types of VDCC was investigated in freshly isolated human interlobular arteries. High K + led to a dose‐dependent constriction of the arteries. Nifedipine blocked the K + (70 mM) induced constriction with an EC50 of 1.2 × 10 −8 M. Blockade of T‐type channels by mibefradil inhibited the constriction with an EC50 of 6.8 × 10 −7 M. The response was very variable between individual patients. Blocking P/Q‐type channels using ω‐agatoxin IVA (10 −8 nmol/L) had no significant effect (14.8 ± 5.0 % decrease) on the constriction. We conclude that all human renal arteries express functionally significant L‐type, VDCC while there is a more variable presence and significance of P/Q‐ and T‐type VDCC. Research Support: Lundbeck Foundation, Danish Medical Research Council, Danish Heart Foundation