Suppression of voltage-dependent K+ currents in retinal bipolar cells by ascorbate

1999 ◽  
Vol 16 (1) ◽  
pp. 141-148 ◽  
Author(s):  
SHIH-FANG FAN ◽  
STEPHEN YAZULLA
Keyword(s):  
Oxidative Stress ◽  
Suppressive Effect ◽  
Bipolar Cells ◽  
High Concentration ◽  
Cell Recording ◽  
Voltage Dependent ◽  
Retinal Bipolar Cells ◽  
K Currents ◽  
Vertebrate Central Nervous System ◽  
Kinase A

Ascorbate, often used as an antioxidant in neural studies, may also serve as a neuromodulator in the vertebrate central nervous system (CNS), in that it modulates the synaptic actions of glutamate and dopamine. Retina of fish contain a high concentration of ascorbate. The release and/or uptake of neurotransmitters are related to membrane potential, which to a large extent is determined by the activity of K+ channels. As retinal bipolar cells are subject to synaptic input from glutamatergic and dopaminergic sources, the effects of ascorbate on voltage-dependent K+ currents (IK(V)) of the mixed rod–cone ON-center bipolar cells (Mb) in goldfish retinal slices were studied using whole-cell recording techniques. IK(V) was suppressed reversibly 60% by 100–200 μM ascorbate. The effect of ascorbate was not due to changes in pH, oxidative stress, lipid peroxidation, any Ca2+-dependent or Na+-dependent action. However, the suppressive effect of ascorbate was blocked by cholera toxin and Wiptide, a protein kinase A (PKA) inhibitor. It is concluded that ascorbate, at physiological concentrations, inhibits IK(V) of bipolar cells via a GS-protein-PKA system. This effect of ascorbate should be taken into account when using ascorbate as an antioxidant in retinal studies involving dopamine.

Differential expression of K+ currents in mammalian retinal bipolar cells

2002 ◽  
Vol 19 (2) ◽  
pp. 163-173 ◽  
Author(s):  
HUI-JUAN HU ◽  
ZHUO-HUA PAN
Keyword(s):  
Differential Expression ◽  
Cell Voltage ◽  
Bipolar Cells ◽  
Inactivation Kinetics ◽  
Voltage Dependent ◽  
Retinal Bipolar Cells ◽  
Kinetics Of ◽  
Retinal Cone ◽  
K Currents ◽  
Three Components

Whole-cell voltage-clamp recordings were performed to investigate voltage-dependent K+ currents in acutely isolated retinal cone bipolar cells (CBCs) from the rat. The physiological and pharmacological properties of the currents were compared with those in rod bipolar cells (RBCs). The K+ currents were found to be much larger in CBC than in RBCs. In addition, the currents in CBCs were activated and inactivated at more negative potentials. Based on the apparent inactivation property of the currents, CBCs were found to fall into two groups of cells that differed in the inactivation kinetics of IK(V) but did not correlate to the ON- and OFF-type. The IK(V) for the group of CBCs showing faster inactivation, as well as for all RBCs, contained two components with decay time constants around 0.1 and 1 s. The IK(V) for the group of CBCs showing slower inactivation only contained the slower component. Furthermore, three components of IK(V) were observed based on tetraethylammonium (TEA) sensitivity: high-sensitive, low-sensitive, and resistant component. The IK(V) for a portion of CBCs showing faster inactivation, as well as for all RBCs, contained all three components. The IK(V) for the remaining CBCs, including all of those CBCs showing slower inactivation, only contained the latter two components. This study reveals a differential expression of K+ currents in rat retinal bipolar cells, suggesting that K+ channels may play an important role in bipolar cell processing in mammalian retinas.

Differential Oxidative Modulation of Voltage-Dependent K+ Currents in Rat Hippocampal Neurons

2002 ◽  
Vol 87 (6) ◽  
pp. 2990-2995 ◽  
Author(s):  
Wolfgang Müller ◽  
Katrin Bittner
Keyword(s):  
Hydrogen Peroxide ◽  
Hippocampal Neurons ◽  
Immune Defense ◽  
Delayed Rectifier ◽  
Delayed Rectifier Current ◽  
Cell Recording ◽  
Voltage Dependent ◽  
Steady State Inactivation ◽  
K Currents ◽  
Stimulation Of

Oxidative stress is enhanced by [Ca2+]i-dependent stimulation of phospholipases and mitochondria and has been implicated in immune defense, ischemia, and excitotoxicity. Using whole cell recording from hippocampal neurons, we show that arachidonic acid (AA) and hydrogen peroxide (H2O2) both reduce the transient K+ current I A by −54 and −68%, respectively, and shift steady-state inactivation by −10 and −15 mV, respectively. While AA was effective at an extracellular concentration of 1 μM and an intracellular concentration of 1 pM, extracellular H2O2 was equally effective only at a concentration >800 μM (0.0027%). In contrast to AA, H2O2 decreased the slope of activation and increased the slope of inactivation of I A and reduced the sustained delayed rectifier current I K(V) by 22% and shifted its activation by −9 mV. Intracellular application of the antioxidant glutathione (GSH, 2–5 mM) blocked all effects of AA and the reduction of I A by H2O2. In contrast, intracellular GSH enhanced reduction of I K(V) by H2O2. Decrease of the slope of activation and increase of the slope of inactivation of I A by hydrogen peroxide was blocked and reversed to a decrease, respectively, by intracellular application of GSH. Intracellular GSH did not prevent H2O2 to shift inactivation and activation of I A and activation of I K(V) to more negative potentials. We conclude, that AA and H2O2modulate voltage-activated K currents differentially by oxidation of GSH accessible intracellular and GSH inaccessible extracellular K+-channel domains, thereby presumably affecting neuronal information processing and oxidative damage.

Biphasic modulation of voltage-dependent currents of retinal cones by cannabinoid CB1 receptor agonist WIN 55212-2

2003 ◽  
Vol 20 (2) ◽  
pp. 177-188 ◽  
Author(s):  
SHIH-FANG FAN ◽  
STEPHEN YAZULLA
Keyword(s):  
Receptor Agonist ◽  
Suppressive Effect ◽  
Cannabinoid Cb1 Receptor ◽  
Enhancing Effect ◽  
Voltage Gated ◽  
Voltage Dependent ◽  
The Brain ◽  
Goldfish Retina ◽  
Voltage Activation ◽  
Kinase A

Endogenous cannabinoids modulate neurotransmitter action and release in the brain. The effects are exerted on membrane permeability to Ca2+ and K+via protein kinase A (PKA). Cannabinoid CB1 receptors are present at the synaptic terminals of cones in goldfish retina. We investigated the effects of CB1 receptor agonist WIN 55212-2 on voltage-gated currents of goldfish cones. Whole-cell currents were recorded with conventional-patch-clamp methods in goldfish retinal slices. Depolarizing pulses elicited inward ICa and Ioutward that contained several components: IK, IA, and ICl. WIN 55212-2 (<1 μM) enhanced IK, ICl, and ICa, while at >1 μM, IK, ICl, and ICa were suppressed. The voltage-activation ranges of these currents were not affected. All effects of WIN 55212-2 were blocked by the CB1 receptor antagonist SR 141716A as well as the PKA inhibitor Wiptide. The enhancing effect of WIN 55212-2 was blocked selectively by 0.5 nM cholera toxin and the suppressive effect was blocked by pertussis toxin. The results obtained from long and short single cones and double cones were basically the same.

Spontaneous regenerative activity in mammalian retinal bipolar cells: Roles of multiple subtypes of voltage-dependent Ca2+ channels

2003 ◽  
Vol 20 (2) ◽  
pp. 131-139 ◽  
Author(s):  
YU-PING MA ◽  
ZHUO-HUA PAN
Keyword(s):  
Spontaneous Activity ◽  
Bipolar Cells ◽  
Potential Oscillations ◽  
Regenerative Activity ◽  
Voltage Dependent ◽  
Cell Groups ◽  
Retinal Bipolar Cells ◽  
Ca2 Channels ◽  
Rod Bipolar Cells ◽  
Cone Bipolar Cells

Patch-clamp recordings were used to investigate the properties of the regenerative activity in acutely isolated bipolar cells from the rat retina. Spontaneous, pacemaker-like membrane potential oscillations were observed in all rod bipolar cells and the majority of cone bipolar cells. The waveform of the regenerative potential was stereotypical but distinct among different bipolar cell groups, especially between rod and cone bipolar cells. The spontaneous activity was completely blocked by Co2+, suggesting that Ca2+ influx through voltage-dependent Ca2+ channels was required for initiating such activity. Ca2+-induced Ca2+ release, however, was not found to be involved. The spontaneous activity was also blocked by mibefradil, a T-type Ca2+ channel antagonist. In contrast, application of nimodipine, an L-type Ca2+ current antagonist, affected mainly the waveform of the regenerative potential. This study shows that mammalian retinal bipolar cells in isolation are also capable of generating Ca2+-dependent spontaneous regenerative potential. However, T-type Ca2+ channels appear to be essential for the initiation of the spontaneous activity in mammalian bipolar cells.

scholarly journals Development of Presynaptic Inhibition Onto Retinal Bipolar Cell Axon Terminals Is Subclass-Specific

2008 ◽  
Vol 100 (1) ◽  
pp. 304-316 ◽  
Author(s):  
Timm Schubert ◽  
Daniel Kerschensteiner ◽  
Erika D. Eggers ◽  
Thomas Misgeld ◽  
Martin Kerschensteiner ◽  
...  
Keyword(s):  
Bipolar Cell ◽  
Presynaptic Inhibition ◽  
Synapse Formation ◽  
Critical Role ◽  
Bipolar Cells ◽  
Inhibitory Synapses ◽  
Axon Terminals ◽  
Cell Recording ◽  
Retinal Bipolar Cells ◽  
Cone Bipolar Cells

Synaptic integration is modulated by inhibition onto the dendrites of postsynaptic cells. However, presynaptic inhibition at axonal terminals also plays a critical role in the regulation of neurotransmission. In contrast to the development of inhibitory synapses onto dendrites, GABAergic/glycinergic synaptogenesis onto axon terminals has not been widely studied. Because retinal bipolar cells receive subclass-specific patterns of GABAergic and glycinergic presynaptic inhibition, they are a good model for studying the development of inhibition at axon terminals. Here, using whole cell recording methods and transgenic mice in which subclasses of retinal bipolar cells are labeled, we determined the temporal sequence and patterning of functional GABAergic and glycinergic input onto the major subclasses of bipolar cells. We found that the maturation of GABAergic and glycinergic synapses onto the axons of rod bipolar cells (RBCs), on-cone bipolar cells (on-CBCs) and off-cone bipolar cells (off-CBCs) were temporally distinct: spontaneous chloride-mediated currents are present in RBCs earlier in development compared with on- and off-CBC, and RBCs receive GABAergic and glycinergic input simultaneously, whereas in off-CBCs, glycinergic transmission emerges before GABAergic transmission. Because on-CBCs show little inhibitory activity, GABAergic and glycinergic events could not be pharmacologically distinguished for these bipolar cells. The balance of GABAergic and glycinergic input that is unique to RBCs and off-CBCs is established shortly after the onset of synapse formation and precedes visual experience. Our data suggest that presynaptic modulation of glutamate transmission from bipolar cells matures rapidly and is differentially coordinated for GABAergic and glycinergic synapses onto distinct bipolar cell subclasses.

Three distinct G protein pathways mediate inhibition of neuronal calcium current by bradykinin

1996 ◽  
Vol 76 (5) ◽  
pp. 3559-3562 ◽  
Author(s):  
M. A. Wilk-Blaszczak ◽  
W. D. Singer ◽  
F. Belardetti
Keyword(s):  
G Protein ◽  
G Proteins ◽  
Pertussis Toxin ◽  
Calcium Current ◽  
Suppressive Effect ◽  
Calcium Currents ◽  
Tetraacetic Acid ◽  
Combined Application ◽  
Voltage Dependent ◽  
K Currents

1. In NG108-15 cells dialyzed with 10 mM ethylene glycolbis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) or bis (o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA), bradykinin (BK) selectively inhibited the N-type calcium current. This effect of BK was blocked by an antibody directed against the G protein G13. Thus under these conditions G13 mediates the inhibition of voltage-dependent calcium current (ICa, V) by BK. In contrast, activation of K+ currents by BK is mediated by Gq/11. BK also couples to Gi2. 2. We now examine the involvement of G proteins in the inhibition of ICa, V by BK when NG108-15 cells are dialyzed with 1 mM BAPTA. Under these conditions, BK inhibited both the N- and L-type, but not the T-type, calcium currents. Intracellular application of anti-G13 antibody did not suppress the response to BK. Applications of either anti-Gq/11 antibody or pertussis toxin (PTX, to block Gi2) were similarly ineffective. Even combined application of anti-Gq/11 and -G13 antibodies, or PTX together with either antibody, did not block inhibition of ICa, V by BK. However, the combination of both antibodies with PTX blocked the response to BK in low BAPTA. In conclusion, both Gq/11 and a PTX-sensitive G protein (presumably Gi2), together with G13, are involved in the inhibition of ICa, V by BK. 3. Gq/11 inhibited only the L-type calcium current, whereas the PTX-sensitive G protein inhibited both the N- and L-type calcium currents. 4. The BAPTA dependence of the Gq/11 and PTX-sensitive inhibitions may reflect a Ca2+ requirement of the pathway(s) acting on the L current and/or a direct suppressive effect of BAPTA.

Calcium channel and prolactin release in rat clonal pituitary cells: effects of verapamil

1982 ◽  
Vol 243 (1) ◽  
pp. E68-E73
Author(s):  
S. Ozawa ◽  
N. Kimura
Keyword(s):  
Suppressive Effect ◽  
Gh3 Cells ◽  
Pituitary Cells ◽  
Ca Current ◽  
High Concentration ◽  
Prolactin Release ◽  
Delayed Rectification ◽  
High K ◽  
Maximum Rate Of Rise ◽  
K Currents

Effects of verapamil on membrane electrical properties and prolactin release were studied in a rat anterior pituitary cell line GH3. Thyrotropin-releasing hormone (TRH), Ba2+, and high concentration of K+ enhance the release of prolactin from GH3 cells. These stimulatory actions on prolactin release were inhibited by adding 10(-4) M verapamil to the bathing mediums. The maximum rate of rise of the Ca action potential was reduced to 17% of the control by addition of 10(-4) M verapamil. Ba2+ caused a sustained membrane depolarization because Ba2+ goes through the Ca channels and blocks the development of the delayed rectification. This effect of Ba2+ was also inhibited by verapamil. Verapamil suppressed both the Na+ and outward K+ currents in addition to the Ca2+ current. The suppressive effect of verapamil on the voltage-sensitive Ca current is probably responsible for the inhibition of TRH- and high K+-stimulated prolactin release because the suppression of the Na+ and outward K+ currents does not inhibit the stimulatory actions of these secretagogues

Voltage-Dependent Na+ Currents in Mammalian Retinal Cone Bipolar Cells

2000 ◽  
Vol 84 (5) ◽  
pp. 2564-2571 ◽  
Author(s):  
Zhuo-Hua Pan ◽  
Hui-Juan Hu
Keyword(s):  
Time Course ◽  
Cell Function ◽  
Signal Transmission ◽  
Bipolar Cells ◽  
Whole Cell Patch Clamp ◽  
Na Currents ◽  
Voltage Dependent ◽  
Steady State Inactivation ◽  
Retinal Bipolar Cells ◽  
Cone Bipolar Cells

Voltage-dependent Na+ channels are usually expressed in neurons that use spikes as a means of signal coding. Retinal bipolar cells are commonly thought to be nonspiking neurons, a category of neurons in the CNS that uses graded potential for signal transmission. Here we report for the first time voltage-dependent Na+ currents in acutely isolated mammalian retinal bipolar cells with whole cell patch-clamp recordings. Na+ currents were observed in ∼45% of recorded cone bipolar cells but not in rod bipolar cells. Both on and off cone bipolar cells were found to express Na+ channels. The Na+ currents were activated at membrane potentials around −50 to −40 mV and reached their peak around −20 to 0 mV. The half-maximal activation and steady-state inactivation potentials were −24.7 and −68.0 mV, respectively. The time course of recovery from inactivation could be fitted by two time constants of 6.2 and 81 ms. The amplitude of the Na+ currents ranged from a few to >300 pA with the current density in some cells close or comparable to that of retinal third neurons. In current-clamp recordings, Na+-dependent action potentials were evoked in Na+-current-bearing bipolar cells by current injections. These findings raise the possibility that voltage-dependent Na+ currents may play a role in bipolar cell function.

Mammalian Retinal Bipolar Cells Express Inwardly Rectifying K+ Currents (IKir) With a Different Distribution Than That of Ih

2003 ◽  
Vol 90 (5) ◽  
pp. 3479-3489 ◽  
Author(s):  
Yu-Ping Ma ◽  
Jinjuan Cui ◽  
Hui-Juan Hu ◽  
Zhuo-Hua Pan
Keyword(s):  
Bipolar Cells ◽  
Patch Clamp Recording ◽  
Functional Roles ◽  
Whole Cell Patch Clamp ◽  
Physiological Properties ◽  
Retinal Bipolar Cells ◽  
Inwardly Rectifying ◽  
K Currents ◽  
Rod Bipolar Cells ◽  
Cone Bipolar Cells

Retinal bipolar cells comprise multiple subtypes that are well known for the diversity of their physiological properties. We investigated the properties and functional roles of the hyperpolarization-activated currents in mammalian retinal bipolar cells using whole cell patch-clamp recording techniques. We report that bipolar cells express inwardly rectifying K+ currents ( IKir) in addition to the hyperpolarization-activated cationic currents ( Ih) previously reported. Furthermore, these two currents are differentially expressed among different subtypes of bipolar cells. One group of cone bipolar cells in particular displayed mainly IKir. A second group of cone bipolar cells displayed both currents but with a much larger Ih. Rod bipolar cells, on the other hand, showed primarily Ih. Moreover, we showed that IKir and Ih differentially influence the voltage responses of bipolar cells: Ih facilitates and/or accelerates the membrane potential rebound, whereas IKir counteracts or prevents such rebound. The findings of the expression of IKir and the differential expression of Ih and IKir in bipolar cells may provide new insights into an understanding of the physiological properties of bipolar cells.

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