Reduction of [Ca(2+)](i) restores uncoupled beta-adrenergic signaling in isolated perfused transgenic mouse hearts

The effects of alterations in calcium in the perfusion media were studied on ss-adrenergic coupling in isolated hearts from 3 different transgenic mice: cardiac-specific overexpressed alpha(1) subunit of L-type calcium channel, overexpressed Galpha(q), and phospholamban knockout. Isolated hearts from all 3 models, when studied at [Ca(2+)] of 2 mmol/L in the perfusate, showed the usual blunted or no response to ss-adrenergic stimulation. Lowering [Ca(2+)] to 0.75 to 1.5 mmol/L unloaded the hearts of calcium and restored to nearly normal the responsiveness to ss-agonist stimulation.