Potentiation of BK Channels by α5β1 Integrin Activation in Arteriolar Smooth Muscle

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.