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Emerging Concepts in Ion Channel Biophysics
Poster Abstracts
57
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.