| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1F Calcium Channel Subunit in the Rat Retina
From the John Curtin School of Medical Research, Australian National University, Canberra.
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
1F calcium channel subunit
cause incomplete X-linked congenital stationary night blindness
(CSNB2), the phenotype of which is consistent with a defect in
neurotransmission within the retina. The purpose of this study was to
determine the cellular distribution of the 1F subunit in
the retina.
METHODS. Antibodies were raised against a unique peptide from the human
1F sequence. Rat retina sections were labeled with
affinity-purified 1F antibodies and the
immunofluorescence analyzed by confocal microscopy. The
1F staining was compared with that obtained with a
pan-1 antibody, used to reveal the distribution of known
voltage-gated calcium channels in the retina. Some sections were double
labeled for 1F and the photoreceptor synaptic ribbon
marker, bassoon.
RESULTS. Staining of retina sections with anti-1F resulted in
strong punctate labeling in the outer plexiform layer (OPL) and weak
punctate labeling in the inner plexiform layer (IPL), consistent with a
synaptic localization. Staining was also observed in the outer nuclear
layer. Within the OPL, 1F immunoreactivity was clustered
in discrete, horseshoe-shaped patches, the shape and dimensions of
which are characteristic of rod active zones. Similar structures were
labeled with the pan-1 antibody. Localization of
1F immunoreactivity to rod active zones was confirmed by
double labeling for bassoon, a component of photoreceptor synaptic
ribbons.
CONCLUSIONS. The distribution of 1F immunoreactivity in the OPL
suggests that calcium influx through 1F or
1F-like channels mediates glutamate release from rod
photoreceptors.
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
As at conventional synapses, neurotransmitter release at ribbon synapses is triggered by the influx of calcium through voltage-gated calcium channels. The electrophysiological properties of the calcium channels and their distribution within the nerve terminal are likely to be key determinants of the release properties of a synapse. The calcium channels at phasic synapses in the brain have been well characterized molecularly and physiologically. They open at relatively high voltages and can be physically associated with docked synaptic vesicles.6 7 These properties result in tight temporal coupling of transmitter release to action potentials.
The calcium currents of fish and amphibian photoreceptors are sensitive
to dihydropyridines (DHPs); thus, they have been classified as
L-type.8
9
10
Localization of 1C
calcium channel subunits to the synaptic layers of the salamander
retina suggests that L-type channels mediate transmitter release in the
amphibian retina.11
In contrast, both the molecular
identity and subcellular distribution of the calcium channels of
mammalian photoreceptors are unknown. The calcium currents of cone
photoreceptors in the tree shrew, and monkey retinas have been
characterized electrophysiologically and appear similar to L-type
currents, although the activation threshold is more hyperpolarized and
the DHP sensitivity lower than for other L-type
channels.12
13
The synaptic terminals of long-wavelength
cones in the tree shrew retina can be labeled with antibodies against
the 1D subunit of brain L-type calcium
channels, but staining is absent from short-wavelength cones and
rods.13
14
Recently, a novel calcium channel gene, CACNA1F, was
identified that encodes the 1 subunit of a
retina-specific, voltage-gated calcium channel,
1F.15
16
Sequence comparisons
show that 1F is a member of the L-type family
of 1 subunits, displaying the greatest amino
acid identity (62%) to the 1D subunit of
brain L-type calcium channels.15
16
Mutations in
CACNA1F cause incomplete X-linked congenital stationary
night blindness (CSNB2), a recessive nonprogressive visual disease, the
phenotype of which is consistent with a defect in neurotransmission
within the retina between the photoreceptors and second-order
neurons.17
The present work shows that 1F
immunoreactivity is localized to photoreceptor cell bodies and the
synaptic terminals of rod photoreceptors in the rat retina. Moreover,
it appears to be colocalized with rod active zones, implicating
1F or 1F-like
channels in the release of glutamate at this synapse.
Preliminary results of this work have been reported in abstract form.18
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
1F Antiserum1F antiserum was
performed by Chiron Technologies (Melbourne, Australia), as described
previously.19
Sheep were immunized with a peptide
corresponding to amino acids 712 to 730 of human
1F (peptide sequence: SNEKDLPQENEGLVPGVEK)
coupled through an additional C-terminal cysteine to diptheria toxoid
(DT). Immune serum was collected after two immunizations and stored at
-20°C. Anti-1F antibodies were affinity
purified against 1 mg 1F peptide coupled to
an N-hydroxysuccinimide (NHS)-activated affinity
column (HiTrap; Amersham Pharmacia Biotech, Uppsala, Sweden) according
to the manufacturer’s protocol.
Preparation of Retina Sections
Wistar Kyoto rats 6 to 8 weeks of age were killed by injection
with an overdose of pentobarbital and the eyes removed. The eyes were
cut in half and posterior eyecups fixed in 4% (wt/vol)
paraformaldehyde in phosphate-buffered saline (PBS) for 5 to 15 minutes
for 1F staining or 4% (wt/vol) carbodiimide
in phosphate buffer (PB) for 30 minutes for
pan-1 staining. The eyecups were cryoprotected
in sucrose, embedded in optimal cutting temperature (OCT) compound
(Sakura Finetek, Torrence, CA) and sectioned at 12-µm thickness on a
cryostat. Sections were collected on gelatin-coated slides, air-dried,
and stored at -20°C. All animals were used in compliance with the
ARVO Statement for the Use of Animals in Ophthalmic and Vision
Research.
Immunofluorescence Microscopy
Retina sections were blocked by incubation for 30 minutes at
room temperature (RT) in antibody incubation solution (AIS; 0.5%
Triton X-100, 5% horse serum, 0.05% NaN3 in
PBS). Sections were then incubated in the primary antibody diluted in
AIS for either 2 hours or overnight at RT. The sections were washed
three times in PBS and then incubated for 1 hour at RT in the secondary
antibody diluted in AIS. Sections were again washed in PBS and then
coverslipped with Mowiol (Hoechst, Strasbourg, Germany). The following
primary antibodies were used at the indicated dilutions:
anti-1F (1:103),
anti-pan-1 (1:50; Alomone Laboratories,
Jerusalem, Israel), and anti-bassoon (1:10; StressGen Biotechnologies
Corp., Victoria, British Columbia, Canada). The following secondary
antibodies were used (all from Jackson ImmunoResearch Laboratories,
West Grove, PA): donkey anti-sheep-IgG coupled to
carboxymethylindocyanine (Cy3; 1:500), goat-anti-rabbit-IgG-Cy3
(1:500), goat-anti-mouse-IgG-Cy3 (1:500), and donkey-anti-sheep-IgG
coupled to fluorescein isothiocyanate (FITC; 1:50). The sections were
analyzed with a confocal laser scanning microscope (model TCS 4D;
Leica, Heidelberg, Germany) outfitted with a x40 1.4 numerical
aperture oil immersion objective. In the double-labeling experiments,
neither cross-labeling of secondary antibodies nor bleed-through
between the two filter sets was observed. Images of single optical
sections of approximately 0.5-µm thickness were collected and
imported into image analysis software for editing (Adobe Photoshop, San
Jose, CA). Image enhancement was limited to minor adjustments to image
brightness, which were made uniformly over the entire image.
Western Blot Analysis
Rats were anesthetized with a lethal intraperitoneal injection
of pentobarbital and their retinas removed. Subcellular retina
fractions were prepared by adapting the protocol of Muresan et
al.,20
as follows. All steps were performed at
0oC to 4oC. Two rat retinas
were immersed in 750 µl ice-cold PB buffer (15 mM phosphate buffer
[pH 7.4], 1 mM MgCl2, 1 mM EGTA, and 0.025%
NaN3). A protease-inhibitor cocktail (50 µl;
4-(2-aminoethyl)benzenesulfonyl fluoride [AEBSF], pepstatin
A, E-64, bestatin, leupeptin, aprotinin; Sigma Chemical Co., St. Louis,
MO) was added to the buffer (PB) and the tissue was homogenized by hand
with 40 up-and-down strokes in a 1-ml glass homogenizer with a Teflon
pestle. The homogenate was layered over 500 µl 50% sucrose in PB in
a 1.5-ml microcentrifuge tube and centrifuged for 10 min at
15,000g, 4°C in a microcentrifuge (Heraeus Amersil,
Duluth, GA). The membrane fraction at the buffer–sucrose interface was
collected and suspended in 1x SDS sample buffer. Proteins were
separated by SDS-polyacrylamide gel electrophoresis on precast 4% to
12% Bis-Tris gels (Novex; San Diego, CA) and immunoblotted using
chemiluminescent detection (ECL; Amersham International, Amersham, UK)
as previously described.19
Antibodies were used at the
following concentrations: 1:1000 anti-1F
(human;), and 1:5000 donkey anti-sheep IgG coupled to horseradish
peroxidase (HRP; Jackson ImmunoResearch Laboratories).
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
1 antibody recognizing the highly
conserved ß-subunit binding site on calcium channel
1 subunits was used to reveal the localization
of voltage-activated calcium channels in the rat retina (Fig. 1)
. At low power the pan-1 antibody
predominantly stained the synaptic layers of the retina, the outer
plexiform layer (OPL), and the inner plexiform layer (IPL). The
staining of both plexiform layers appeared punctate, consistent with
the localization of calcium channels to retinal
synapses.21
In addition to the synaptic staining, the
pan-1 antibody labeled the photoreceptor inner
segments and, faintly, the neuronal cell bodies in the inner (INL) and
outer (ONL) nuclear layers. All pan-1 staining
was blocked by preincubation of the antibody with the peptide antigen
(not shown).
|
1
staining were observed in the OPL, appearing as numerous elliptical
puncta and sparser, large patches (Fig. 1B)
. Some of the
pan-1 puncta were crescent-shaped (Fig. 1C)
.
Rods, which constitute approximately 99% of the photoreceptors in the
rat retina,22
have a single active zone, whereas the less
numerous cones have larger terminals and, in the primate retina,
contain 20 to 30 active zones.23
24
Thus, it is possible
that the large patches of pan-1 staining
correspond to cone terminals and the smaller puncta to rod terminals.
Distribution of 1F Immunoreactivity in the Rat
Retina
Affinity-purified 1F antibodies against a
unique peptide derived from the human 1F
sequence15
16
were used to determine the distribution of
1F-like calcium channels in the rat retina. On
a Western blot of rat retinal membranes, these antibodies labeled two
prominent bands of 142 and 150 kDa and fainter bands at 125 and 170 kDa
(Fig. 2D)
. Preincubation of the antibody with the 1F
peptide completely blocked these bands, thus demonstrating specificity
(not shown). Immunofluorescent staining of vertical retina sections
with anti-1F resulted in intense staining of
the OPL and fainter staining of the IPL (Fig. 2B)
. The
1F staining in the IPL, compared with that in
the OPL, was somewhat fainter and sparser than was the
pan-1 staining, suggesting that the
1F immunoreactivity may be localized to a
subset of IPL synapses. Faint 1F staining was
also observed over the ONL. The specificity of the
1F labeling was confirmed by complete block of
the staining by preincubation of the antibody with the
1F peptide (Fig. 2C)
and by the absence of
staining with the preimmune serum (data not shown).
|
1F Immunoreactivity in the OPL1F antibody labeled horseshoe-shaped
structures approximately 2 µm in length, characteristic of rod active
zones as defined by the synaptic ribbons.25
The horseshoe
shapes of the 1F staining in the OPL suggest
that, rather than being diffusely distributed on the plasma membrane of
the rod spherule, the calcium channels are closely associated with the
active zone beneath the single synaptic ribbon of the rod
photoreceptor. Labeling with the pan-1
antibody confirmed the presence of calcium channels associated with
these structures (Fig. 1C)
. Because of the low proportion of cone
photoreceptors in the rodent retina, it was less clear whether they
were also labeled with anti-1F. The large
patches of staining, possibly corresponding to cone terminals, seen
with the pan-1 antibody (Fig. 1)
, were not
observed with the 1F antibody (Figs. 3A
3B)
.
A few aggregates of 1F staining were seen
(Fig. 3B
, arrowheads) in which discrete horseshoe shapes could not be
distinguished. These 1F aggregates may reside
in cone terminals, which contain more numerous but smaller active zones
than rods, although they are smaller than the patches detected by the
pan-1 antibody.
|
1F immunoreactivity to rod
active zones was confirmed by double labeling retina sections with the
1F antibody and an antibody against the active
zone marker, bassoon. Bassoon is a 420-kDa protein that is a component
of the presynaptic density in conventional synapses, but that has been
localized by immunoelectron microscopy to the base of photoreceptor
synaptic ribbons in the OPL of the rat retina.26
The
1F and bassoon immunoreactivities were
localized to similar horseshoe-shaped structures in the OPL. The two
staining patterns partially overlapped in the OPL (Fig. 4)
, demonstrating close apposition of the calcium channels with rod
photoreceptor active zones.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
1F calcium channel subunit,
has been identified as the site of mutations causing CSNB2 in
humans.15
16
The phenotype of the disease implicates the
1F calcium channel in neurotransmission
between photoreceptors and inner retinal neurons. Previous work by
Morgans et al. (manuscript submitted) shows that at least two
1F isoforms or
1F-like channels are present in the retina,
one localized to photoreceptor cell bodies and the other to the OPL.
The antibody used in the present study labels both the OPL and
photoreceptor cell bodies. This study compares the distribution of
1F immunoreactivity to the total distribution
of calcium channel 1 subunits in the rat
retina and shows that 1F immunoreactivity in
the OPL is localized to the active zones of rod photoreceptors.
Detailed reconstruction of the rod terminal shows that rods have a
single linear active zone approximately 2 µm long that curves around
an invagination of the presynaptic plasma membrane into which the
postsynaptic elements protrude.25
Curving over the length
of the active zone is the synaptic ribbon, an electron-dense, platelike
structure to which numerous synaptic vesicles are
tethered.25
At high magnification, the
1F immunofluorescence in the OPL (Figs. 3
4)
appeared to consist mainly of numerous horseshoe-shaped arcs
approximately 2 µm long. The 1F
immunostaining in the OPL was very similar to that observed for
proteins associated with photoreceptor synaptic ribbons:
KIF3A,27
rab interacting molecule (Rim),28
B16,29
30
and bassoon.26
This highly
characteristic staining pattern is a strong indication that the
1F immunoreactivity is associated with the rod
active zone. This is confirmed in Figure 4
by the overlap between
1F staining in the OPL and staining for the
active zone marker, bassoon, located at the base of synaptic ribbons in
photoreceptors.26
It was less obvious whether cone terminals in the rod-dominated rat
retina22
were labeled with the 1F
antibody. Unlike the single, large active zone of the rod terminal,
cones contain numerous, smaller active zones clustered at the base of
the terminal. The pan-1 antibody, which
recognizes all known high-voltage–activated (HVA) calcium channels,
would be expected to label both rod and cone terminals. Similar to the
1F staining in the OPL, the
pan-1 antibody labeled arcs approximately
2-µm long, characteristic of rod active zones (Fig. 1)
. In addition,
the pan-1 antibody stained sparsely
distributed, large patches that are putative cone terminals, based on
their low ratio to the small puncta (
1:40–1:80, depending on the
tissue section). The 1F antibody also labeled
occasional aggregates of smaller puncta that may have been cone
terminals, but these patches were smaller than those labeled with the
pan-1 antibody. The difference in the
pan-1 and 1F staining
in the OPL suggests that cone terminals may contain additional calcium
channels that are recognized by the pan-1, but
not the 1F antibody. Heterogeneity among
photoreceptor calcium channels has been described previously in the
tree shrew retina14
where the synaptic terminals of long
wavelength cones were labeled with an 1D
subunit antibody, whereas short-wavelength cones and rods were not.
The molecular identity of photoreceptor calcium channels may differ
across species. This is suggested by comparison of the present findings
with those of Nachman-Clewner et al.11
demonstrating immunoreactivity to 1C subunits
in photoreceptor terminals in the salamander retina. Within the
terminals of dissociated photoreceptors, the
1C staining appeared in hot spots, possibly
representing active zones. Differences in the L-type channels expressed
by mammalian and amphibian photoreceptors may underlie the apparent
differences in the DHP sensitivity of their respective calcium
currents.8
10
12
13
Nachman-Clewner et al.11
also show 1C immunoreactivity in the OPL of
the rat retina, although it is not clear whether the staining is in
photoreceptor terminals or horizontal cell dendrites, and the
specificity of the staining in rat tissue is not demonstrated.
The localization of 1F immunoreactivity to
rod, and possibly cone, active zones implicates
1F or 1F-like
channels in the release of glutamate from photoreceptors. If
1F were the only presynaptic calcium channel
in rod terminals, loss-of-function mutations might be expected to
eliminate synaptic transmission from rods and result in complete night
blindness, rather than the incomplete night-blind phenotype of
CSNB2.17
The absence of 1F
activity during development in individuals with CSNB2 may lead to
changes in retinal circuitry that partially compensate for the absence
of transmission from rods. For instance, an upregulation of gap
junctions between rods and cones might allow the rod signal to be
partially transmitted through cones. This could explain the elevated
stimulus threshold and delay of the scotopic threshold response (STR)
associated with CSNB2.31
The 1F
immunoreactivity in the ONL suggests that the
1F channel serves an additional function in
retinal physiology, besides mediating transmitter release, which may
also contribute to the CSNB2 phenotype.
The finding that 1F immunoreactivity is
closely associated with the synaptic ribbon in the rod photoreceptor,
rather than being diffusely distributed around the synaptic terminal,
argues for the plasma membrane at the base of the ribbon being the
primary, if not the sole, site of neurotransmitter release. The
restriction of the calcium channels to the active zone suggests that
they are anchored in place, perhaps as a component of a macromolecular
active zone complex, the analysis of which should yield further insight
into organization and function of the neurotransmitter release
machinery of the ribbon synapse.
|
Acknowledgements |
|---|
|
Footnotes |
|---|
Submitted for publication November 15, 2000; revised February 26 and May 1, 2001; accepted May 25, 2001.
Commercial relationships policy: N.
The publication costs of this article were defrayed in part by page
charge payment. This article must therefore be marked
"advertisement" in accordance with 18 U.S.C. 
1734
solely to indicate this fact.
Corresponding author: Catherine W. Morgans, Synaptic Biochemistry Group, Division of Neuroscience, John Curtin School of Medical Research, Canberra, ACT, 2600, Australia. catherine.morgans{at}anu.edu.au
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
1-subunit gene in Xp11.23 cause incomplete X-linked congenital stationary night blindness Nat Genet 19,264-267[Medline][Order article via Infotrieve]
1F calcium channel in the rodent retina Soc Neurosci Abstr 25,1432
This article has been cited by other articles:
|
|
 |
|
  F. Haeseleer Interaction and Colocalization of CaBP4 and Unc119 (MRG4) in Photoreceptors Invest. Ophthalmol. Vis. Sci., June 1, 2008; 49(6): 2366 - 2375. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Lee, A. Jimenez, G. Cui, and F. Haeseleer Phosphorylation of the Ca2+-Binding Protein CaBP4 by Protein Kinase C {zeta} in Photoreceptors J. Neurosci., November 14, 2007; 27(46): 12743 - 12754. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Okawa and A. P. Sampath Optimization of Single-Photon Response Transmission at the Rod-to-Rod Bipolar Synapse Physiology, August 1, 2007; 22(4): 279 - 286. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Almanza, F. Navarrete, R. Vega, and E. Soto Modulation of Voltage-Gated Ca2+ Current in Vestibular Hair Cells by Nitric Oxide J Neurophysiol, February 1, 2007; 97(2): 1188 - 1195. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R Jalkanen, M Mantyjarvi, R Tobias, J Isosomppi, E-M Sankila, T Alitalo, and N T Bech-Hansen X linked cone-rod dystrophy, CORDX3, is caused by a mutation in the CACNA1F gene J. Med. Genet., August 1, 2006; 43(8): 699 - 704. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Maeda, J. Lem, K. Palczewski, and F. Haeseleer A Critical Role of CaBP4 in the Cone Synapse Invest. Ophthalmol. Vis. Sci., November 1, 2005; 46(11): 4320 - 4327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Doering, J. Hamid, B. Simms, J. E. McRory, and G. W. Zamponi Cav1.4 Encodes a Calcium Channel with Low Open Probability and Unitary Conductance Biophys. J., November 1, 2005; 89(5): 3042 - 3048. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Mansergh, N. C. Orton, J. P. Vessey, M. R. Lalonde, W. K. Stell, F. Tremblay, S. Barnes, D. E. Rancourt, and N. T. Bech-Hansen Mutation of the calcium channel gene Cacna1f disrupts calcium signaling, synaptic transmission and cellular organization in mouse retina Hum. Mol. Genet., October 15, 2005; 14(20): 3035 - 3046. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Reim, H. Wegmeyer, J. H. Brandstatter, M. Xue, C. Rosenmund, T. Dresbach, K. Hofmann, and N. Brose Structurally and functionally unique complexins at retinal ribbon synapses J. Cell Biol., May 23, 2005; 169(4): 669 - 680. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Hosoi, I. Arai, and M. Tachibana Group III Metabotropic Glutamate Receptors and Exocytosed Protons Inhibit L-Type Calcium Currents in Cones But Not in Rods J. Neurosci., April 20, 2005; 25(16): 4062 - 4072. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Zhang, A. Beuve, and E. Townes-Anderson The Nitric Oxide-cGMP Signaling Pathway Differentially Regulates Presynaptic Structural Plasticity in Cone and Rod Cells J. Neurosci., March 9, 2005; 25(10): 2761 - 2770. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Cia, A. Bordais, C. Varela, V. Forster, J. A. Sahel, A. Rendon, and S. Picaud Voltage-Gated Channels and Calcium Homeostasis in Mammalian Rod Photoreceptors J Neurophysiol, March 1, 2005; 93(3): 1468 - 1475. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Claes, M. Seeliger, S. Michalakis, M. Biel, P. Humphries, and S. Haverkamp Morphological Characterization of the Retina of the CNGA3-/-Rho-/- Mutant Mouse Lacking Functional Cones and Rods Invest. Ophthalmol. Vis. Sci., June 1, 2004; 45(6): 2039 - 2048. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. McRory, J. Hamid, C. J. Doering, E. Garcia, R. Parker, K. Hamming, L. Chen, M. Hildebrand, A. M. Beedle, L. Feldcamp, et al. The CACNA1F Gene Encodes an L-Type Calcium Channel with Unique Biophysical Properties and Tissue Distribution J. Neurosci., February 18, 2004; 24(7): 1707 - 1718. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Baumann, A. Gerstner, X. Zong, M. Biel, and C. Wahl-Schott Functional Characterization of the L-type Ca2+ Channel Cav1.4{alpha}1 from Mouse Retina Invest. Ophthalmol. Vis. Sci., February 1, 2004; 45(2): 708 - 713. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Palmer, C. Hull, J. Vigh, and H. von Gersdorff Synaptic Cleft Acidification and Modulation of Short-Term Depression by Exocytosed Protons in Retinal Bipolar Cells J. Neurosci., December 10, 2003; 23(36): 11332 - 11341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Barnes Center-surround Antagonism Mediated by Proton Signaling at the Cone Photoreceptor Synapse J. Gen. Physiol., November 24, 2003; 122(6): 653 - 656. [Full Text] [PDF]
|
|
|
|
|
|
M. A. Khodair, M. A. Zarbin, and E. Townes-Anderson Synaptic Plasticity in Mammalian Photoreceptors Prepared as Sheets for Retinal Transplantation Invest. Ophthalmol. Vis. Sci., November 1, 2003; 44(11): 4976 - 4988. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Koschak, D. Reimer, D. Walter, J.-C. Hoda, T. Heinzle, M. Grabner, and J. Striessnig Cav1.4{alpha}1 Subunits Can Form Slowly Inactivating Dihydropyridine-Sensitive L-Type Ca2+ Channels Lacking Ca2+-Dependent Inactivation J. Neurosci., July 9, 2003; 23(14): 6041 - 6049. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kreft, D. Krizaj, S. Grilc, and R. Zorec Properties of Exocytotic Response in Vertebrate Photoreceptors J Neurophysiol, July 1, 2003; 90(1): 218 - 225. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Vigh, E. Solessio, C. W. Morgans, and E. M. Lasater Ionic Mechanisms Mediating Oscillatory Membrane Potentials in Wide-Field Retinal Amacrine Cells J Neurophysiol, July 1, 2003; 90(1): 431 - 443. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nakamura, S. Ito, C.-H. Piao, H. Terasaki, and Y. Miyake Retinal and Optic Disc Atrophy Associated With a CACNA1F Mutation in a Japanese Family Arch Ophthalmol, July 1, 2003; 121(7): 1028 - 1033. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Zenisek, V. Davila, L. Wan, and W. Almers Imaging Calcium Entry Sites and Ribbon Structures in Two Presynaptic Cells J. Neurosci., April 1, 2003; 23(7): 2538 - 2548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Heidelberger, Z.-Y. Zhou, and G. Matthews Multiple Components of Membrane Retrieval in Synaptic Terminals Revealed by Changes in Hydrostatic Pressure J Neurophysiol, November 1, 2002; 88(5): 2509 - 2517. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Schwartz Transport-Mediated Synapses in the Retina Physiol Rev, October 1, 2002; 82(4): 875 - 891. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Zhang and E. Townes-Anderson Regulation of Structural Plasticity by Different Channel Types in Rod and Cone Photoreceptors J. Neurosci., August 15, 2002; 22(16): 7065 - 7079. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Heidelberger, P. Sterling, and G. Matthews Roles of ATP in Depletion and Replenishment of the Releasable Pool of Synaptic Vesicles J Neurophysiol, July 1, 2002; 88(1): 98 - 106. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
). (C) High-magnification image of
pan-
