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Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10676-81. Epub 2003 Sep 4.

Calcium regulation of the soluble adenylyl cyclase expressed in mammalian spermatozoa.

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  • 1Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305-5317, USA.


In mammals, Ca2+ and HCO3- ions play a critical role in the regulation of sperm function, most likely by regulation of cAMP levels. Mammalian germ cells contain a soluble adenylyl cyclase (sAC) with properties distinct from the well characterized membrane-bound enzymes Here we investigated whether the cyclase expressed in mature spermatozoa has the properties of sAC and whether it is regulated by Ca2+. In addition to an HCO3--dependent activation, the cyclase endogenous to human spermatozoa is stimulated 2- to 3-fold by Ca2+ in a concentration-dependent manner (EC50 approximately 400 nM). In a similar fashion, Ca2+ activates the recombinant rat and human full-length sAC with similar EC50 values. The Ca2+ stimulation was also observed when sAC was activated with HCO3-, was independent of calmodulin, and was associated with an increase in Vmax without changes in Km for ATP-Mg2+. An increase in intracellular Ca2+ by ionophore or by a muscarinic cholinergic receptor agonist increases cAMP in cells transfected with FL-hsAC, but not in mock-transfected cells. Similarly, both Ca2+ and HCO3- stimulate cAMP accumulation in human spermatozoa. These findings provide evidence that human spermatozoa express a cyclase with the properties of sAC and that Ca2+ can substitute for HCO3- in the stimulation of this enzyme, underscoring an important role for sAC in the control of sperm functions.

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