%0 Journal Article %A Jean-Charles Hoda %A Francesca Zaghetto %A Alexandra Koschak %A Jörg Striessnig %T Congenital Stationary Night Blindness Type 2 Mutations S229P, G369D, L1068P, and W1440X Alter Channel Gating or Functional Expression of Cav1.4 L-type Ca2+ Channels %D 2005 %R 10.1523/JNEUROSCI.3054-04.2005 %J The Journal of Neuroscience %P 252-259 %V 25 %N 1 %X Mutations in the CACNA1F gene (voltage-dependent L-type calcium channel α1F subunit) encoding retinal Cav1.4 L-type Ca2+ channels cause X-linked recessive congenital stationary night blindness type 2 (CSNB2). Many of them are predicted to yield nonfunctional channels. Complete loss of Cav1.4 function is therefore regarded as a pathogenetic mechanism for the impaired signaling from photoreceptors to second-order retinal neurons. We investigated the functional consequences of CSNB2 missense mutations S229P, G369D, and L1068P and the C-terminal truncation mutant W1440X. After expression in Xenopus laevis oocytes or human embryonic kidney tsA-201 cells, inward Ca2+ current (ICa) and inward Ba2+ current (IBa) could be recorded from mutations G369D and L1068P. G369D shifted the half-maximal voltage for channel activation (V0.5,act) significantly to more negative potentials (>11 mV), slowed inactivation, and removed Ca2+-dependent inactivation. The L1068P mutant yielded currents only in the presence of the channel activator BayK8644. Currents (IBa) inactivated faster than wild type (WT) and recovered more slowly from inactivation (IBa and ICa). No channel activity could be measured for mutants S229P and W1440X after oocyte expression. No W1440X α1 protein was detected after expression in tsA-201 cells, whereas S229P (as well as G369D and L1068P) α1 subunits were expressed at levels indistinguishable from WT (n = 3). Our data provide unequivocal evidence that CSNB2 missense mutations can induce severe changes in Cav1.4 function, which may decrease (L1068P and S229P) or even increase (G369D) channel activity. The lower activation range of G369D can explain the reduced dynamic range of photoreceptor signaling. Moreover, we demonstrate that loss of channel function of one (L1068P) CSNB2 mutation can be rescued by a Ca2+ channel activator. %U https://www.jneurosci.org/content/jneuro/25/1/252.full.pdf