Calmodulin: a new partner for the α 1A ‐adrenergic receptor

In addition to its role in vasoconstriction, the α 1A ‐adrenergic receptor (α 1A ‐AR) is increasingly recognized as a rescue mechanism under circumstances where b‐ARs are insufficient to provide stimulus in the myocardium, such as in heart failure. Mechanisms controlling α 1A ‐AR function therefore have profound impact on cardiovascular functions. Calmodulin (CaM) is the ubiquitous transducer of Ca 2+ signals, and has recently been demonstrated to interact with a number of G protein‐coupled receptors. We have observed that in fresh ventricular tissues, α 1A ‐AR forms a complex with calmodulin in resting condition as well as under α 1A ‐AR agonism. To identify and characterize the precise interaction domains between CaM and α 1A ‐AR, we developed novel biosensors that span multiple fragments of the four sub‐membrane domains (SMDs) of α 1A ‐AR. Responses of these biosensors to Ca 2+ ‐saturated CaM reveals that α 1A ‐AR directly interacts with CaM at a number of locations with disparate affinities and Ca 2+ sensitivities. These data implicate CaM as a novel partner for α 1A ‐AR and provide background for on‐going studies on the functional impact of these interactions in the control of cardiovascular functions.