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J Neurosci
2005 Jan 05;251:252-9. doi: 10.1523/JNEUROSCI.3054-04.2005.
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Congenital stationary night blindness type 2 mutations S229P, G369D, L1068P, and W1440X alter channel gating or functional expression of Ca(v)1.4 L-type Ca2+ channels.
Hoda JC
,
Zaghetto F
,
Koschak A
,
Striessnig J
.
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Mutations in the CACNA1F gene (voltage-dependent L-type calcium channel alpha1F subunit) encoding retinal Ca(v)1.4 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 Ca(v)1.4 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 (I(Ca)) and inward Ba2+ current (I(Ba)) could be recorded from mutations G369D and L1068P. G369D shifted the half-maximal voltage for channel activation (V(0.5,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 (I(Ba)) inactivated faster than wild type (WT) and recovered more slowly from inactivation (I(Ba) and I(Ca)). No channel activity could be measured for mutants S229P and W1440X after oocyte expression. No W1440X alpha1 protein was detected after expression in tsA-201 cells, whereas S229P (as well as G369D and L1068P) alpha1 subunits were expressed at levels indistinguishable from WT (n = 3). Our data provide unequivocal evidence that CSNB2 missense mutations can induce severe changes in Ca(v)1.4 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.
P 17109-B05 Austrian Science Research Fund, P 17109-B05 Austrian Science Fund FWF, P 17109 Austrian Science Fund FWF, FWF_P 17109 Austrian Science Fund FWF
Ball,
Role of the beta(2) subunit of voltage-dependent calcium channels in the retinal outer plexiform layer.
2002, Pubmed
Ball,
Role of the beta(2) subunit of voltage-dependent calcium channels in the retinal outer plexiform layer.
2002,
Pubmed
Barnes,
Calcium channels at the photoreceptor synapse.
2002,
Pubmed
Baumann,
Functional characterization of the L-type Ca2+ channel Cav1.4alpha1 from mouse retina.
2004,
Pubmed
Bech-Hansen,
Loss-of-function mutations in a calcium-channel alpha1-subunit gene in Xp11.23 cause incomplete X-linked congenital stationary night blindness.
1998,
Pubmed
Boycott,
Clinical variability among patients with incomplete X-linked congenital stationary night blindness and a founder mutation in CACNA1F.
2000,
Pubmed
Castellano,
Cloning and expression of a third calcium channel beta subunit.
1993,
Pubmed
,
Xenbase
Catterall,
Structure and regulation of voltage-gated Ca2+ channels.
2000,
Pubmed
Corey,
The calcium current in inner segments of rods from the salamander (Ambystoma tigrinum) retina.
1984,
Pubmed
Dunlap,
Identification of calcium channels that control neurosecretion.
1994,
Pubmed
Ellis,
Sequence and expression of mRNAs encoding the alpha 1 and alpha 2 subunits of a DHP-sensitive calcium channel.
1988,
Pubmed
Hess,
Calcium channel selectivity for divalent and monovalent cations. Voltage and concentration dependence of single channel current in ventricular heart cells.
1986,
Pubmed
Horton,
Engineering hybrid genes without the use of restriction enzymes: gene splicing by overlap extension.
1989,
Pubmed
Huber,
Conserved Ca2+-antagonist-binding properties and putative folding structure of a recombinant high-affinity dihydropyridine-binding domain.
2000,
Pubmed
Kors,
Delayed cerebral edema and fatal coma after minor head trauma: role of the CACNA1A calcium channel subunit gene and relationship with familial hemiplegic migraine.
2001,
Pubmed
Koschak,
Cav1.4alpha1 subunits can form slowly inactivating dihydropyridine-sensitive L-type Ca2+ channels lacking Ca2+-dependent inactivation.
2003,
Pubmed
Krieg,
Functional messenger RNAs are produced by SP6 in vitro transcription of cloned cDNAs.
1984,
Pubmed
,
Xenbase
Liang,
Unified mechanisms of Ca2+ regulation across the Ca2+ channel family.
2003,
Pubmed
McRory,
The CACNA1F gene encodes an L-type calcium channel with unique biophysical properties and tissue distribution.
2004,
Pubmed
Morgans,
Expression of the alpha1F calcium channel subunit by photoreceptors in the rat retina.
2001,
Pubmed
Morgans,
Neurotransmitter release at ribbon synapses in the retina.
2000,
Pubmed
Moriondo,
Calcium-activated potassium current clamps the dark potential of vertebrate rods.
2001,
Pubmed
Murakami,
Antinociceptive action of amlodipine blocking N-type Ca2+ channels at the primary afferent neurons in mice.
2001,
Pubmed
Perez-Reyes,
Cloning and expression of a cardiac/brain beta subunit of the L-type calcium channel.
1992,
Pubmed
,
Xenbase
Platzer,
Congenital deafness and sinoatrial node dysfunction in mice lacking class D L-type Ca2+ channels.
2000,
Pubmed
Safayhi,
L-type calcium channels in insulin-secreting cells: biochemical characterization and phosphorylation in RINm5F cells.
1997,
Pubmed
Schneeweis,
Noise and light adaptation in rods of the macaque monkey.
2000,
Pubmed
Shi,
Molecular determinants of voltage-dependent slow inactivation of the Ca2+ channel.
2002,
Pubmed
,
Xenbase
Splawski,
Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism.
2004,
Pubmed
,
Xenbase
Stotz,
Functional roles of cytoplasmic loops and pore lining transmembrane helices in the voltage-dependent inactivation of HVA calcium channels.
2004,
Pubmed
Strom,
An L-type calcium-channel gene mutated in incomplete X-linked congenital stationary night blindness.
1998,
Pubmed
Tremblay,
The electroretinographic diagnosis of the incomplete form of congenital stationary night blindness.
1995,
Pubmed
Wilkinson,
The dihydropyridine-sensitive calcium channel subtype in cone photoreceptors.
1996,
Pubmed
Witkovsky,
Gain of rod to horizontal cell synaptic transfer: relation to glutamate release and a dihydropyridine-sensitive calcium current.
1997,
Pubmed
,
Xenbase
Yamaguchi,
Key roles of Phe1112 and Ser1115 in the pore-forming IIIS5-S6 linker of L-type Ca2+ channel alpha1C subunit (CaV 1.2) in binding of dihydropyridines and action of Ca2+ channel agonists.
2003,
Pubmed
Yang,
Molecular determinants of Ca2+ selectivity and ion permeation in L-type Ca2+ channels.
1993,
Pubmed
,
Xenbase
Zamponi,
Regulation of presynaptic calcium channels by synaptic proteins.
2003,
Pubmed