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The stress hormone norepinephrine increases the rate and strength of heart muscle contraction during the fight-or-flight response. The increase in strength is largely due to up-regulation of the activity of the cardiac Ca v1.2 by norepinephrine ( 7). Because of the central physiological role and hence the long-lasting interest in and focus on the regulation of Ca v1.2, it is considered one of the holy grails of channel regulation. The timely work of Liu et al. ( 8) delineated one major regulatory mechanism in heart muscle. They found that stimulation of β-adrenergic receptors (β ARs) by no...