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Potentiation of BK Channels by α5β1 Integrin Activation in Arteriolar Smooth Muscle
Author(s) -
Davis Michael John,
Yang Yan,
Wu Xin,
Gui Peichun,
Sohma Yoshiro,
Meininger Gerald A,
Davis George E,
Braun Andrew P
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.1145.3
Subject(s) - chemistry , iberiotoxin , integrin , patch clamp , vasodilation , myocyte , vascular smooth muscle , biophysics , bk channel , microbiology and biotechnology , membrane potential , endocrinology , smooth muscle , cell , receptor , biochemistry , biology
RGD peptides produce sustained vasodilation of rat skeletal muscle arterioles. We hypothesized that RGD ligands work through α5β1 integrin to modulate the activity of large conductance, Ca 2+ ‐activated K + (BK) channels in arteriolar smooth muscle. K + currents were recorded in single arteriolar myocytes using whole‐cell and single‐channel patch clamp methods. Activation of α5β1 integrin by an insoluble antibody resulted in ∼30–50% increase in the amplitude of IBTX‐sensitive, whole‐cell K + current. The endogenous α5β1 integrin ligand, fibronectin (FN; 10 μg/ml, 120 kD fragment), potentiated IBTX‐sensitive K + current by ∼80%, an effect that was blocked by the c‐Src inhibitor, PP2 (0.1–1 μM). In cell‐attached or excised, inside‐out patches, the N•Po of a ∼240 pS K + channel was significantly increased after FN application to the external surface of the patch through the recording pipette. FN also caused a leftward shift in the N•Po‐voltage relationship at constant [Ca 2+ ], which was blocked by PP2. The results suggest that α5β1 integrin activation potentiates BK channel activity in vascular smooth muscle via a membrane‐delimited pathway through both Ca 2+ ‐ and c‐Src‐dependent mechanisms.