Abstract 11905: Loss of Adrenergic and Adenosine Regulation of Extradyadic L-type Calcium Channels in Rat Atrial Myocytes in Heart Failure

• DOI: 10.1161/circ.132.suppl_3.11905
• Publication Date: 2024-04-23T10:56:22Z
• Authors: Alexey V Glukhov; Marina Balycheva; Jose Sanchez-Alonso; Navneet Bhogal; Ivan Diakonov; Marta Mazzola; Giuseppe Faggian; Julia Gorelik
• Keywords: L-type calcium channel

It has recently become evident that discrete clusters of L-type Ca2+ channels (LTCCs) exist along the cardiomyocyte sarcolemma in association with distinct membrane structures. Such microdomain-specific localization impact channel function and regulation by a variety neurohormonal pathways, including adrenergic adenosine. Disruption their subcellular targeting may contribute to pathophysiology cardiac diseases, heart failure (HF). We used imaging super-resolution scanning patch clamp examine LTCCs atrial myocytes isolated from control 16-weeks post-MI HF rats. In control, β1 receptors (β1ARs) stimulation (ISO 100 nM β2AR antagonist ICI 50 nM) enhanced spontaneous release events while following adenosine A1 (AdoA1Rs) (2'-MeCCPA 200 abolished β1ARs effects. Non-localized 2 μM external solution) activated single both t-tubules on crest sarcolemma, increasing LTCC occurrence enhancing open probability amplitude. Local AdoA1R through pipette (10 μM) β1ARs-pretreated cells completely HF, effects were preserved lost crest. Similar, effect β1AR was significantly reduced (28% vs 134% P<0.01) anti-adrenergic (8% 84% P<0.01), despite up-regulation AdoA1Rs mRNA. No changes caveolae density observed (4.6±0.4 caveolae/μm 3.7±0.5 for P=0.167). Our findings provide first direct evidence remodeling which could be linked local disruption interactions between cellular microenvironment. This extends beyond classical concept electrical remodeling, stressing involvement alteration spatial compartmentation ion addition concepts protein expression post-translational modifications.