Laminin binding to β1‐integrins selectively alters β1‐ and β2‐adrenoceptor signalling in cat atrial myocytes

Abstract

1 Perforated patch recordings were used to determine how plating atrial cells on laminin alters β-adrenergic receptor (β-AR) regulation of L-type Ca²⁺ current (I_Ca,L). 2 Isoproterenol (isoprenaline; ISO; 0.01 μM), a non-selective β-AR agonist, elicited a greater stimulation of I_Ca,L in cells plated on laminin (+79 ± 16 %; n= 17) than on glass (+33 ± 5 %; n= 23). Also, desensitization to ISO was greater in cells on laminin (−16 ± 2 %) than on glass (−3 ± 1 %). Atenolol (0.1 μM), a selective β₁-AR antagonist, inhibited the effects of ISO in cells on glass but not laminin. Conversely, 0.1 μM ICI 118,551, a selective β₂-AR antagonist, inhibited the effects of ISO in cells on laminin but not glass. With β₂-ARs blocked, ISO-induced stimulation of I_Ca,L was greater in cells on glass than laminin. 3 Zinterol (0.01–0.1 μM), a selective β₂-AR agonist, elicited a greater stimulation of I_Ca,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,L was greater in cells plated on an αβ₁-integrin antibody than on glass. Also, addition of 20 μM cytochalasin D to cells on laminin prevented the enhanced effects of ISO typically elicited in cells on laminin alone. 5 We conclude that laminin binding to αβ₁-integrins, in conjunction with the actin cytoskeleton, reduces β₁-AR and enhances β₂-AR signalling which regulates I_Ca,L. This novel mechanism may contribute to remodelling of β-AR signalling in the failing heart.