Plating cat atrial myocytes on laminin elicited a greater stimulation of L-type Ca2+ current by isoproterenol (+79%) compared to cells plated on glass (+33%).
Laminin binding to alpha-beta1-integrins selectively alters beta-adrenergic receptor signaling in cat atrial myocytes, which may contribute to remodeling in the failing heart.
Absolute Event Rate: 79% vs 33%
Perforated patch recordings were used to determine how plating atrial cells on laminin alters beta-adrenergic receptor (beta-AR) regulation of L-type Ca2+ current (ICa,L). 2. Isoproterenol (isoprenaline; ISO; 0.01 microM), a non-selective beta-AR agonist, elicited a greater stimulation of ICa,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 microM), a selective beta1-AR antagonist, inhibited the effects of ISO in cells on glass but not laminin. Conversely, 0.1 microM ICI 118,551, a selective beta2-AR antagonist, inhibited the effects of ISO in cells on laminin but not glass. With beta2-ARs blocked, ISO-induced stimulation of ICa,L was greater in cells on glass than laminin. 3. Zinterol (0.01-0.1 microM), a selective beta2-AR agonist, elicited a greater stimulation of ICa,L in cells on laminin than on glass. The effects of zinterol were blocked by ICI 118,551. 4. ISO-induced stimulation of ICa,L was greater in cells plated on an alphabeta1-integrin antibody than on glass. Also, addition of 20 microM 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 alphabeta1-integrins, in conjunction with the actin cytoskeleton, reduces beta1-AR and enhances beta2-AR signalling which regulates ICa,L. This novel mechanism may contribute to remodelling of beta-AR signalling in the failing heart.
Wang et al. (Tue,) conducted a other in Cat atrial myocytes. Plating on laminin vs. Plating on glass was evaluated on Stimulation of L-type Ca2+ current (ICa,L) by isoproterenol. Plating cat atrial myocytes on laminin elicited a greater stimulation of L-type Ca2+ current by isoproterenol (+79%) compared to cells plated on glass (+33%).