Laminin binding to beta(1)-integrins selectively alters beta(1)- and beta(2)-adrenoceptor signalling in eat atrial myocytes

1. Perforated patch recordings were used to determine how plating atrial ce lls on laminin alters beta-adrenergic receptor (beta-AR) regulation of L-ty pe Ca2+ current (I-Ca,I-L). 2. Isoproterenol (isoprenaline; ISO; 0.01 mu M), a non-selective beta-AR ag onist, elicited a greater stimulation of I-Ca,I-L in cells plated on lamini n (+79 +/- 16%; n = 17) than on glass (+33 +/- 5%; n = 23). Also, desensiti zation to ISO was greater in cells on laminin (-16 +/- 2%) than on glass (- 3 +/- 1%). Atenolol (0.1 mu M), a selective beta(1)-AR antagonist, inhibite d the effects of ISO in cells on glass but not laminin. Conversely, 0.1 mu M ICI 118,551, a selective beta(2)-AR antagonist, inhibited the effects of ISO in cells on laminin but not glass. With beta(2)-ARs blocked, ISO-induce d stimulation of I-Ca,I-L was greater in cells on glass than laminin. 3. Zinterol (0.01-0.1 mu M), a selective beta(2)-AR agonist, elicited a gre ater stimulation of I-Ca,I-L in cells on laminin than on glass. The effects of zinterol were blocked by ICI 118,551. 4. ISO-induced stimulation of I-Ca,I-L was greater in cells plated on an al pha beta(1)-integrin antibody than on glass. Also, addition of 20 mu M cyto chalasin D to cells on laminin prevented the enhanced effects of ISO typica lly elicited in cells on laminin alone. 5. We conclude that laminin binding to alpha beta(1)-integrins, in conjunct ion with the actin cytoskeleton, reduces beta(1)-AR and enhances beta(2)-AR signalling which regulates I-Ca,I-L. This novel mechanism may contribute t o remodelling of beta-AR signalling in the failing heart.