Loss of annexin A7 leads to alterations in frequency-induced shortening ofisolated murine cardiomyocytes

Annexin A7 has been proposed to function in the fusion of vesicles, acting as a Ca2+ channel and as Ca2+-activated GTPase, thus inducing Ca2+/GTP-depe ndent secretory events. To understand the function of annexin A7, we have p erformed targeted disruption of the Anxa7 gene in mice. Matings between het erozygous mice produced offspring showing a normal Mendelian pattern of inh eritance, indicating that the loss of annexin A7 did not interfere with via bility in utero. Mice lacking annexin A7 showed no obvious phenotype and we re fertile. To assay for exocytosis, insulin secretion from isolated islets of Langerhans was examined. Ca2+-induced and cyclic AMP-mediated potentiat ion of insulin secretion was unchanged in the absence of annexin A7, sugges ting that it is not directly implicated in vesicle fusion. Ca2+ regulation studied in isolated cardiomyocytes, showed that while cells from early embr yos displayed intact Ca2+ homeostasis and expressed all of the components r equired for excitation-contraction coupling, cardiomyocytes from adult Anra 7(-/-) mice exhibited an altered cell shortening-frequency relationship whe n stimulated with high frequencies. This suggests a function for annexin A7 in electromechanical coupling, probably through Ca2+ homoeostasis.