Emerging Concepts in Ion Channel Biophysics

Emerging Concepts in Ion Channel Biophysics

Poster Abstracts

55-POS Board 55 Mibefradil and NNC55-0396 Alkalinize the Mouse Sperm Acrosome Causing Ca 2+ Release Possibly Involving the IP3R Enrique Ismael Oliver Santiago 2 , Alberto Darszon 1 . 1 Instituto de Biotecnología/UNAM, Cuernavaca, Morelos, Mexico, 2 Universidad Autonoma del Estado de Morelos, Cuernavaca, Morelos, Mexico. Ca 2+ plays a pivotal role in fertilization participating in the main functions of mammalian sperm such as maturation, motility, and acrosome reaction (AR). The AR involves the exocytosis of the acrosomal vesicle in response to different physiological and non-physiological stimuli, and is essential for fertilization. The acrosome vesicle contains hydrolytic enzymes that allow sperm to break down extracellular glycoprotein matrixes, is an intracellular Ca 2+ store and its luminal pH (pHa) is very acidic (pH 5.3). Its similarities with endolisosomal systems has led researchers to consider the acrosome as a lysosome-related organelle. Ca 2+ efflux and osmoregulation are key elements of the AR, however, our knowledge about the role of pHa and the molecular identity and functional role of ion channels controlling Ca 2+ efflux from this important organelle is limited. Previous evidence from our laboratory indicated that Mibefradil (10 M) and NNC55-0396 (10 M), both weak bases and blockers of CatSper, a sperm specific Ca 2+ channel, elevate pHa and cause an increase in intracellular Ca 2+ concentration ([Ca 2+] i) in mouse and human sperm. These blockers also induce the AR. Our findings suggested that pHa alkalization regulates acrosomal Ca 2+ transporters that release Ca 2+ leading to [Ca 2+] i increases essential for sperm AR. Here we show that Mibefradil and NNC55-0396 trigger a Xestospongin C (1 M) sensitive Ca 2+ release from the acrosome. These findings suggest that the IP3R present in the acrosome participates in the Ca 2+ release from this organelle induced by its alkalinization triggered by weak bases such as Mibefradil and NNC55-0396.

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