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At least 109 records · Page 6Linked to original sources
PubMed1993

Pharmacology of GABA receptor Cl- channels in rat retinal bipolar cells.

gamma-Aminobutyric acid (GABA), a major inhibitory neurotransmitter in the mammalian nervous system, is known to operate bicuculline-sensitive Cl- channels through GABAA receptors and bicuculline-insensitive cation channels through GABAB receptors. Recent observations indicate that the retina may contain GABA receptors with unusual pharmacological properties. Here we report that GABA gates bicuculline-insensitive Cl- channels in rod bipolar cells of the rat retina, which were not modulated by flunitrazepam, pentobarbital and alphaxalone and were only slightly blocked by picrotoxinin. Moreover, the GABAB receptor agonist baclofen, and the antagonist 2-hydroxysaclofen had no effect. The underlying single-channel conductance was 7 pS and the open time 150 ms. These values are clearly different from those obtained for GABAA receptor channels recorded in other neurons of the same preparation, and in other parts of the brain. The bicuculline- and baclofen-insensitive GABA receptors were activated selectively by the GABA analogue cis-4-aminocrotonic acid (CACA). Hence they may be similar to those receptors termed GABAC receptors.

Animals↗
PubMed2001

Calcium influx selects the fast mode of endocytosis in the synaptic terminal of retinal bipolar cells.

To investigate the regulation of endocytosis by Ca(2+), we have made capacitance measurements in the synaptic terminal of depolarizing bipolar cells from the retina of goldfish. After a brief depolarization, all of the excess membrane was retrieved rapidly (tau approximately 1 s). But when the rise in free [Ca(2+)] was reduced by the introduction of Ca(2+) buffers [1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate (BAPTA) or EGTA], a large fraction of the membrane was retrieved by a second, slower mechanism (tau > or = 10 s). The block of fast endocytosis by EGTA could be overcome by increasing the amplitude of the Ca(2+) current, demonstrating that Ca(2+) influx was the trigger for fast endocytosis. These manipulations of the Ca(2+) signal altered the relative proportions of fast and slow endocytosis but did not modulate the rate constants of these processes. A brief stimulus that triggered fast endocytosis did not generate a significant rise in the spatially averaged [Ca(2+)], indicating that Ca(2+) regulated endocytosis through an action close to the active zone. The slow mode of retrieval occurred at the resting [Ca(2+)]. These results demonstrate that Ca(2+) influx couples fast endocytosis and exocytosis at this synapse.

Buffers↗
PubMed1991

Glutamate and 2-amino-4-phosphonobutyrate evoke an increase in potassium conductance in retinal bipolar cells.

Although there is general agreement that L-glutamate can produce a depolarizing inward current to account for the hyperpolarizing (OFF) bipolar cell response, the conductance mechanism underlying the depolarizing (ON) response has been difficult to establish satisfactorily. To investigate the ionic bases of the center responses, we studied the whole-cell currents controlled by L-glutamate and its analogues in solitary bipolar cells from salamander retina. We report here two groups of isolated bipolar cells: one group responded to L-glutamate with the previously described inward current [Attwell, D., Mobbs, P., Tessier-Lavigne, M. & Wilson, M. (1987) J. Physiol. (London) 387, 125-161] and a second group showed an outward current that reversed at about -70 mV. Both were associated with an increase in membrane conductance. In addition, DL-2-amino-4-phosphonobutyrate, a compound diagnostic for ON-bipolar cell activity [Slaughter, M. M. & Miller, R. F. (1981) Science 211, 182-185], elicited outward currents that closely resembled those seen in response to L-glutamate and, furthermore, that were shown to arise from an increase in conductance to potassium ions. Thus the presence of two distinct conductances controlled by L-glutamate in solitary cells would provide one mechanism for generating the ON and OFF light responses at the bipolar cell level in the intact retina.

Ambystoma↗
PubMed1998

Calcium and protein kinase C regulate the actin cytoskeleton in the synaptic terminal of retinal bipolar cells.

The organization of filamentous actin (F-actin) in the synaptic pedicle of depolarizing bipolar cells from the goldfish retina was studied using fluorescently labeled phalloidin. The amount of F-actin in the synaptic pedicle relative to the cell body increased from a ratio of 1.6 +/- 0.1 in the dark to 2.1 +/- 0.1 after exposure to light. Light also caused the retraction of spinules and processes elaborated by the synaptic pedicle in the dark. Isolated bipolar cells were used to characterize the factors affecting the actin cytoskeleton. When the electrical effect of light was mimicked by depolarization in 50 mM K+, the actin network in the synaptic pedicle extended up to 2.5 micrometer from the plasma membrane. Formation of F-actin occurred on the time scale of minutes and required Ca2+ influx through L-type Ca2+ channels. Phorbol esters that activate protein kinase C (PKC) accelerated growth of F-actin. Agents that inhibit PKC hindered F-actin growth in response to Ca2+ influx and accelerated F-actin breakdown on removal of Ca2+. To test whether activity-dependent changes in the organization of F-actin might regulate exocytosis or endocytosis, vesicles were labeled with the fluorescent membrane marker FM1-43. Disruption of F-actin with cytochalasin D did not affect the continuous cycle of exocytosis and endocytosis that was stimulated by maintained depolarization, nor the spatial distribution of recycled vesicles within the synaptic terminal. We suggest that the actions of Ca2+ and PKC on the organization of F-actin regulate the morphology of the synaptic pedicle under varying light conditions.

Actins↗
PubMed1988

Membrane currents in retinal bipolar cells of the axolotl.

By whole-cell patch-clamping bipolar cells isolated from enzymatically dissociated retinae, we have studied the nonsynaptic ionic currents that may play a role in shaping the bipolar cell light response and in determining the level of voltage noise in these cells. Between -30 and -70 mV, the membrane current of isolated bipolar cells is time independent, and the input resistance is 1-2 G omega. Depolarization past -30 mV activates an outward current (in less than 100 ms), which then inactivates slowly (approximately 1 s). Inactivation of this current is removed by hyperpolarization over the range -20 to -80 mV. This current is carried largely by K ions. It is not activated by internal Ca2+. The membrane current of isolated bipolar cells is noisy, and the variance of this noise has a minimum between -40 and -60 mV. At its minimum, the standard deviation of the voltage noise produced by nonsynaptic membrane currents is at least 100 microV. The membrane currents of depolarizing bipolar cells in slices of retina were investigated by whole-cell patch-clamping. Their membrane properties were similar to those of isolated bipolar cells, but with a larger membrane capacitance and a smaller input resistance. Their membrane current noise also showed a minimum near -40 to -60 mV. The time-dependent potassium current in axolotl bipolar cells is not significantly activated in the physiological potential range and can therefore play little role in shaping the bipolar cells' voltage response to light. Differences in the waveform of the light response of bipolar cells and photoreceptors must be ascribed to shaping by the synapses between these cells. The noise minimum in the bipolar membrane current is near the dark potential of these cells, and this may be advantageous for the detection of weak signals by the bipolar cells.

Adenosine Triphosphate↗
PubMed1997

Desensitizing GABAC receptors on carp retinal bipolar cells.

Bicuculline- and baclofen-insensitive GABA receptors (GABAC receptors) on bipolar cells acutely dissociated from carp retina were investigated with using the whole-cell patch-clamp recording technique. The currents of these cells mediated by GABAC receptors showed striking desensitization, even at low concentrations of GABA. Both the time constant tau of the GABAC current decay and the extent of desensitization were significantly different from that of GABAC receptors previously observed in other retinas and elsewhere in the CNS, suggesting that the GABAC receptors of carp bipolar cells might be distinct in intracellular mechanisms and subunit composition.

Animals↗
PubMed1999

The kinetics of exocytosis and endocytosis in the synaptic terminal of goldfish retinal bipolar cells.

1. The kinetics of exocytosis and endocytosis were studied in the giant synaptic terminal of depolarizing bipolar cells from the goldfish retina. Two techniques were applied: capacitance measurements of changes in membrane surface area, and fluorescence measurements of exocytosis using the membrane dye FM1-43. 2. Three phases of exocytosis occurred during maintained depolarization to 0 mV. The first component was complete within about 10 ms and involved a pool of 1200-1800 vesicles (with a total membrane area equivalent to about 1.6 % of the surface of the terminal). The second component of exocytosis involved the release of about 4400 vesicles over 1 s. The third component of exocytosis was stimulated continuously at a rate of about 1000 vesicles s-1. 3. After short depolarizations (< 200 ms), neither the FM1-43 signal nor the capacitance signal continued to rise, indicating that exocytosis stopped rapidly after closure of Ca2+ channels. The fall in capacitance could therefore be used to monitor endocytosis independently of exocytosis. The capacitance measured after brief stimuli began to fall immediately, recovering to the pre-stimulus baseline with a rate constant of 0.8 s-1. 4. The amount of exocytosis measured using the capacitance and FM1-43 techniques was similar during the first 200 ms of depolarization, suggesting that the most rapidly released vesicles could be detected by either method. 5. After a few seconds of continuous stimulation, the net increase in membrane surface area reached a plateau at about 5 %, even though continuous exocytosis occurred at a rate of 0.9 % s-1. Under these conditions of balanced exocytosis and endocytosis, the rate constant of endocytosis was about 0.2 s-1. The average rate of endocytosis during maintained depolarization was therefore considerably slower than the rate observed after a brief stimulus. 6. After longer depolarizations (> 500 ms), both the capacitance and FM1-43 signals continued to rise for periods of seconds after closure of Ca2+ channels. The continuation of exocytosis was correlated with a persistent increase in [Ca2+]i in the synaptic terminal, as indicated by the activation of a Ca2+-dependent conductance and measurements of [Ca2+]i using the fluorescent indicator furaptra. 7. The delayed fall in membrane capacitance after longer depolarizations occurred along a double exponential time course indicating the existence of two endocytic processes: fast endocytosis, with a rate constant of 0.8 s-1, and slow endocytosis, with a rate constant of 0.1 s-1. 8. Increasing the duration of depolarization caused an increase in the fraction of membrane recovered by slow endocytosis. After a 100 ms stimulus, all the membrane was recycled by fast endocytosis, but after a 5 s depolarization, about 50 % of the membrane was recycled by slow endocytosis. 9. These results demonstrate the existence of fast and slow endocytic mechanisms at a synapse and support the idea that prolonged stimulation leads to an increase in the amount of membrane retrieved by the slower route. The rise in cytoplasmic Ca2+ that occurred during longer depolarizations was correlated with stimulation of continuous exocytosis and inhibition of fast endocytosis. The results also confirm that transient and continuous components of exocytosis coexist in the synaptic terminal of depolarizing bipolar cells.

Algorithms↗
PubMed1989

Transient calcium current of retinal bipolar cells of the mouse.

1. Isolated bipolar cells were obtained by enzymic (papain) dissociation of the adult mouse retina. The membrane voltage was clamped and the membrane currents were measured by the whole-cell version of the patch-clamp technique. Isolated bipolar cells and horizontal cells of the goldfish retina were also studied for comparison. 2. Hyperpolarization from the holding voltage, Vh, of -46 mV evoked a slowly activating, Cs+-sensitive, inward current (probably an h-current), and depolarization evoked a TEA- and Cs+-sensitive outward current (probably a combination of K+ currents). 3. Depolarization from a more negative Vh (e.g. -96 mV) evoked a transient inward current that had maximal amplitude between -40 and -20 mV. This current was identified as a Ca2+ current (ICa): its amplitude was increased with elevated [Ca2+]o and was decreased with reduced [Ca2+]o, and it was blocked by 4 mM-Co2+, but not by 5 microM-TTX. 4. Both the perikaryon and the axon terminal generated ICa with similar properties. 5. The plot of Ca2+ conductance (gCa) against membrane voltage (activation curve) was sigmoidal: in 10 mM [Ca2+]o, gCa increased for membrane voltages more positive than -65 mV, was half-maximal at about -25 mV, and reached saturation at about +30 mV. The plot of inactivation of gCa against membrane voltage was also sigmoidal: with 1 s conditioning depolarization in 10 mM [Ca2+]o, gCa decreased for membrane voltages more positive than -80 mV, was half-maximal at about -50 mV, and was fully suppressed for voltages greater than -30 mV. 6. ICa in the mouse bipolar cells was insensitive to 50 microM-Cd2+, 10 microM-nifedipine and 10 microM-Bay K 8644. In contrast, the calcium currents of bipolar and horizontal cells of the goldfish retina were markedly suppressed by 50 microM-Cd2+ and 10 microM-nifedipine, and were augmented several fold by 10 microM-Bay K 8644. The calcium currents of goldfish bipolar and horizontal cells were sustained, and were activated in a more positive range of potentials than the ICa of mouse bipolar cells. 7. The voltage range at which the ICa of mouse bipolar cells is activated includes the presumed range of membrane potentials spanned during light-evoked responses; thus, this current may participate in synaptic transmission. The transient character of ICa may also help to shape transient responses of ganglion cells.

Animals↗
PubMed1977

Structural basis for on-and off-center responses in retinal bipolar cells.

Electron microscopy of Golgi preparations of goldfish retina shows that dendrites of type a (hyperpolarizing, off-center) bipolar cells make wide cleft junctions unassociated with synaptic ribbons, while those of type b (depolarizing, on-center) bioplar cells make narrow cleft junctions and synaptic ribbon contacts, with rods and cones. This suggests that wide cleft junctions are the site of sign-conserving, and narrow cleft junctions or ribbon contacts (or both) are the site of sign-inverting synaptic transmission from photoreceptors to bipolars.

Animals↗
PubMed1999

Two actions of calcium regulate the supply of releasable vesicles at the ribbon synapse of retinal bipolar cells.

Ribbon synapses of sensory neurons are able to sustain high rates of exocytosis in response to maintained depolarization, but it is not known how this is achieved. Using the capacitance technique, we have found that Ca(2+) regulates the supply of releasable vesicles at the ribbon synapse of depolarizing bipolar cells from the retina of goldfish. Ca(2+) had two actions that could be differentiated by introduction of the Ca(2+) chelator EGTA; one action stimulated refilling of the rapidly releasable pool of vesicles from a reserve pool, and a second action stimulated recruitment of vesicles to the reserve pool. The capacity of the reserve pool was approximately 3500 vesicles, which is similar to the number that can attach to the ribbons. These results suggest that continuous exocytosis at ribbon synapses is maintained by the Ca(2+)-dependent translocation of vesicles from the cytoplasm, through the ribbon, to release sites on the plasma membrane.

Animals↗
PubMed2000

Synaptic depression and the kinetics of exocytosis in retinal bipolar cells.

The capacitance technique was used to investigate exocytosis at the ribbon synapse of depolarizing bipolar cells from the goldfish retina. When the Ca(2+) current was activated strongly, the rapidly releasable pool of vesicles (RRP) was released with a single rate-constant of approximately 300-500 sec(-1). However, when the Ca(2+) current was activated weakly by depolarization in the physiological range (-45 to -25 mV), exocytosis from the RRP occurred in two phases. After the release of 20% or more of the RRP, the rate-constant of exocytosis fell by a factor of 4-10. Thus, synaptic depression was caused by a reduced sensitivity to Ca(2+) influx, as well as simple depletion of the RRP. In the resting state, the rate of exocytosis varied with the amplitude of the Ca(2+) current raised to the power of 2. In the depressed state, the sensitivity to Ca(2+) influx was reduced approximately fourfold. The initial phase of exocytosis accelerated e-fold for every 2.1 mV depolarization over the physiological range and averaged 120 sec(-1) at -25 mV. The synapse of depolarizing bipolar cells therefore responds to a step depolarization in a manner similar to a high-pass filter. This transformation appears to be determined by the presence of rapidly releasable vesicles with differing sensitivities to Ca(2+) influx. This might occur if vesicles were docked to the plasma membrane at different distances from Ca(2+) channels. These results suggest that the ribbon synapse of depolarizing bipolar cells may be a site of adaptation in the retina.

Animals↗
PubMed2002

Increase in the pool size of releasable synaptic vesicles by the activation of protein kinase C in goldfish retinal bipolar cells.

Secretion from neurons and neuroendocrine cells is enhanced by the activation of protein kinase C (PKC) in various preparations. We have already reported that transmitter (glutamate) release from Mb1 bipolar cells in the goldfish retina is potentiated by the activation of PKC. However, it is not yet settled whether the potentiation is ascribed to the increase in the pool size of releasable synaptic vesicles or in release probability. In the present study, Ca2+ influx and exocytosis were simultaneously monitored by measuring the presynaptic Ca2+ current and membrane capacitance changes, respectively, in a terminal detached from the bipolar cell. The double pulse protocol was used to estimate separately the changes in the pool size and release probability. The activation of PKC by phorbol 12-myristate 13-acetate (PMA) specifically increased the pool size but not the release probability. PKC was activated by PMA even after the Ca2+ influx was blocked by Co2+. In bipolar cells the releasable pool can be divided into two components: one is small and rapidly exhausted, and the other is large and slowly exocytosed. To identify which component is responsible for the increase in the pool size, the effects of PMA and a PKC-specific inhibitor, bisindolylmaleimide I (BIS), on each component were examined. The slow component was selectively increased by PMA and reduced by BIS. Thus, we conclude that the activation of PKC in Mb1 bipolar cells potentiates glutamate release by increasing the pool size of the slow component.

Animals↗
PubMed2003

Synaptic cleft acidification and modulation of short-term depression by exocytosed protons in retinal bipolar cells.

The release of vesicular protons during exocytosis causes a feedback inhibition of Ca2+ channels in photoreceptor terminals; however, the effect of this inhibition on subsequent exocytosis has not been studied. Here we show that a similar L-type Ca2+ channel inhibition occurs in bipolar cell terminals in slices of goldfish retina, and we investigate the effect that this has on subsequent exocytosis with membrane capacitance measurements. We find that transient Ca2+ current inhibition is correlated with exocytosis and modulated by the concentration of extracellular pH buffer. Ca2+ current inhibition is negligible in acutely dissociated terminals, demonstrating the importance of an intact synaptic cleft. The sensitivity of bipolar cell Ca2+ currents to extracellular pH was assessed: channel conductance is reduced and activation is shifted to more positive potentials by acidification. The effect of Ca2+ current inhibition on subsequent exocytosis was investigated by measuring paired-pulse depression. Under conditions in which there is a large amount of inhibition of Ca2+ influx, the degree of paired-pulse depression is significantly reduced. Finally, we show that under physiological (bicarbonate) buffering conditions, pronounced Ca2+ current inhibition occurs after exocytosis ( approximately 60% peak inhibition), which can decrease subsequent exocytosis during single depolarizations. We estimate that exocytosis is accompanied by a transient change in synaptic cleft pH from 7.5 to approximately 6.9. We suggest that this effect serves as an activity-dependent modulator of exocytosis at ribbon-type synapses where a large and compact coterie of vesicles can fuse at each active zone.

Animals↗
PubMed1993

Autoantibodies against retinal bipolar cells in cutaneous melanoma-associated retinopathy.

PURPOSE: This study's goal was to determine the pathophysiology of the retinopathy that occurs in patients with metastatic cutaneous melanoma and sudden onset of night blindness, the so-called melanoma-associated retinopathy (MAR) syndrome. We tested the hypothesis that sera from two MAR patients contained autoantibodies that reacted with "on" bipolar cells of the human retina. METHODS: Immunofluorescence was performed on cryostat sections of unfixed normal human retinas. Sera and IgG fractions were tested from the two MAR patients and 38 control subjects (28 patients with metastatic melanoma, but no visual symptoms; two patients with non-MAR retinopathy; and eight normal subjects). RESULTS: The sera and IgG fractions from both MAR patients but from none of the control subjects produced heavy immunostaining of bipolar cells, which were identified as rod bipolars by a double labeling procedure using anti-protein kinase C. CONCLUSIONS: We hypothesize that MAR patients generate autoantibodies against a melanoma antigen that cross react with bipolar cells of the retina. These antibodies, by an unknown mechanism, may cause abnormalities of the rod and cone systems that are characteristic of MAR.

Adult↗