Nc. Wilkinson et al., EFFECTS OF MECHANO-GATED CATION CHANNEL BLOCKERS ON XENOPUS OOCYTE GROWTH AND DEVELOPMENT, The journal of membrane biology, 165(2), 1998, pp. 161-174
The putative role(s) of a mechanically gated (MG) cation channel in Xe
nopus oocyte growth, maturation, fertilization and embryogenesis has b
een examined. Using a pharmacological approach, we have tested the eff
ects of the MG channel blockers, gadolinium, gen tamicin and amiloride
on the above developmental events. Our results indicate that oocyte m
aturation, fertilization and early embryogenesis (up to the free-swimm
ing stage 45) can proceed normally in the presence of concentrations o
f agents that either completely abolish (i.e., greater than or equal t
o 10 mu M Gd3+) or partially block(i.e., 1 mM gentamicin) single MG ch
annel activity as measured by patch-clamp recording. However, we also
find that higher concentrations of Gd3+ (greater than or equal to 50 m
u M) can lead to an increased percentage (>20%) of axis-perturbed embr
yos compared with control (<1%) and that amiloride (0.5 mM) reduces th
e success of fertilization (from 100% to <50%) and increases mortality
(by similar to 75%) in developing embryos. Furthermore, we find that
all three agents inhibit oocyte growth in vitro. However, their order
of effectiveness (amiloride > gentamicin > Gd3+) is opposite to their
order for blocking MG channels (Gd3+ much greater than gentamicin > am
iloride). These discrepancies indicated that the drugs effects occur b
y mechanisms other than, or in addition to, MG channel block. Our resu
lts provide no compelling evidence for the idea that MG channel activi
ty is critical for development in Xenopus. This could mean that there
are other mechanisms in the oocyte that can compensate when MG channel
activity is blocked or that the protein that forms the channel can un
dergo additional interactions that result in a function insensitive to
MG channel blockers.