scholarly journals Facilitation of T-type calcium current in bullfrog atrial cells: voltage-dependent relief of a G protein inhibitory tone.

1996 ◽  
Vol 491 (2) ◽  
pp. 321-334 ◽  
Author(s):  
J L Alvarez ◽  
L S Rubio ◽  
G Vassort
Keyword(s):  
G Protein ◽  
Calcium Current ◽  
Atrial Cells ◽  
Voltage Dependent ◽  
Inhibitory Tone

Separation and modulation of calcium currents in bullfrog sympathetic neurons

1992 ◽  
Vol 70 (S1) ◽  
pp. S56-S63 ◽  
Author(s):  
Stephen W. Jones ◽  
Keith S. Elmslie
Keyword(s):  
G Protein ◽  
Calcium Current ◽  
Sympathetic Neurons ◽  
Calcium Currents ◽  
Dependent Manner ◽  
Activation Kinetics ◽  
Channel Opening ◽  
Voltage Dependent ◽  
Rapid Activation ◽  
Kinetics Of

The calcium current of frog sympathetic neurons has relatively rapid activation kinetics (τ < 3 ms) in response to changes in voltage. Pharmacologically, the current is blocked ~90% by ω-conotoxin, but < 10% by dihydropyridine antagonists. This suggests that nearly all of the current is N type. However, inactivation is slow and incomplete even for depolarizations lasting > 1 s, consistent with recent evidence that N-type channels do not always inactivate rapidly. The calcium current is partially inhibited via receptors for acetylcholine, luteinizing hormone releasing hormone, substance P, ATP, and norepinephrine. These effects are mimicked by internal dialysis with GTP-γ-S, suggesting involvement of a G protein. The transmitters affect the activation kinetics of the calcium current in a voltage-dependent manner, which can be modeled as a reversible shift of some channels to "reluctant" states in which strong depolarization is needed to produce channel opening. The effects of transmitters develop and recover with t½ ~ 1–2 s, so if a second messenger is involved in receptor – calcium channel coupling, it must act rapidly.Key words: norepinephrine, ω-conotoxin, dihydropyridine, inactivation, G protein.

The G protein G13 mediates inhibition of voltage-dependent calcium current by bradykinin

Neuron ◽  
1994 ◽  
Vol 13 (5) ◽  
pp. 1215-1224 ◽  
Author(s):  
M.A. Wilk-Blaszczak ◽  
W.D. Singer ◽  
S. Gutowski ◽  
P.C. Sternweis ◽  
F. Belardetti
Keyword(s):  
G Protein ◽  
Calcium Current ◽  
Voltage Dependent

G-Protein-Modulated Ca2+ Current With Slowed Activation Does Not Alter the Kinetics of Action Potential-Evoked Ca2+ Current

2000 ◽  
Vol 84 (5) ◽  
pp. 2417-2425 ◽  
Author(s):  
Debra E. Artim ◽  
Stephen D. Meriney
Keyword(s):  
Action Potential ◽  
Calcium Channel ◽  
G Protein ◽  
Calcium Current ◽  
Time Course ◽  
Channel Activation ◽  
Tail Current ◽  
Voltage Dependent ◽  
Dependent Inhibition ◽  
Kinetics Of

We have studied voltage-dependent inhibition of N-type calcium currents to investigate the effects of G-protein modulation-induced alterations in channel gating on action potential-evoked calcium current. In isolated chick ciliary ganglion neurons, GTPγS produced voltage-dependent inhibition that exhibited slowed activation kinetics and was partially relieved by a conditioning prepulse. Using step depolarizations to evoke calcium current, we measured tail current amplitudes on abrupt repolarization to estimate the time course of calcium channel activation from 1 to 30 ms. GTPγS prolonged significantly channel activation, consistent with the presence of kinetic slowing in the modulated whole cell current evoked by 100-ms steps. Since kinetic slowing is caused by an altered voltage dependence of channel activation (such that channels require stronger or longer duration depolarization to open), we asked if GTPγS-induced modulation would alter the time course of calcium channel activation during an action potential. Using an action potential waveform as a voltage command to evoke calcium current, we abruptly repolarized to −80 mV at various time points during the repolarization phase of the action potential. The resulting tail current was used to estimate the relative number of calcium channels that were open. Using action potential waveforms of either 2.2- or 6-ms duration at half-amplitude, there were no differences in the time course of calcium channel activation, or in the percent activation at any time point tested during the repolarization, when control and modulated currents were compared. It is also possible that modulated channels might open briefly and that these reluctant openings would effect the time course of action potential-evoked calcium current. However, when control and modulated currents were scaled to the same peak amplitude and superimposed, there was no difference in the kinetics of the two currents. Thus voltage-dependent inhibition did not alter the kinetics of action potential-evoked current. These results suggest that G-protein-modulated channels do not contribute significantly to calcium current evoked by a single action potential.

Neurotransmitters acting via different G proteins inhibit N-type calcium current by an identical mechanism in rat sympathetic neurons

1995 ◽  
Vol 74 (6) ◽  
pp. 2251-2257 ◽  
Author(s):  
I. Ehrlich ◽  
K. S. Elmslie
Keyword(s):  
Calcium Channels ◽  
G Protein ◽  
G Proteins ◽  
Calcium Current ◽  
Voltage Dependence ◽  
Sympathetic Neurons ◽  
Patch Clamp Technique ◽  
Voltage Dependent ◽  
Dependent Inhibition ◽  
Kinetics Of

1. We studied the mechanism of voltage-dependent inhibition of N-type calcium current by norepinephrine (NE) and vasoactive intestinal peptide (VIP) in adult rat superior cervical ganglion (SCG) neurons using the whole cell patch-clamp technique. 2. The voltage dependence of inhibition is manifest in the reversal of inhibition by strong depolarization. We tested the hypothesis that this voltage dependence results from disruption of G proteins binding to calcium channels. According to this hypothesis, the kinetics of calcium current reinhibition following a strong depolarization should become faster for higher concentrations of active G proteins. 3. Assuming that larger inhibitions result from higher concentrations of active G proteins, we used different concentrations of NE to alter the amplitude of inhibition and, thus, the active G protein concentration. We found that the kinetics of reinhibition at -80 mV following a depolarizing pulse to +80 mV were faster for larger inhibitions. 4. VIP induces voltage-dependent inhibition of N-current via a different G protein (Gs) than that of NE (Go). We found that the effect of VIP on reinhibition kinetics was identical to that produced by NE. 5. Combined application of NE and VIP did not greatly increase the amplitude of the inhibition but significantly increased the rate of reinhibition. Thus NE plus VIP appear to greatly increase the concentration of the molecule binding to the channel (G protein according to the hypothesis). 6. The kinetics of calcium current disinhibition during strong depolarization (step to +80 mV) did not change with the size of the inhibition induced by NE, VIP or application of NE and VIP together. 7. Both the concentration-dependent reinhibition kinetics and concentration-independent disinhibition kinetics are consistent with the hypothesis that active G proteins bind directly to N-type calcium channels to modulate their activity in rat sympathetic neurons.

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.

Reciprocal inhibition of voltage-gated potassium currents (IK(V)) by activation of cannabinoid CB1and dopamine D1receptors in ON bipolar cells of goldfish retina

2005 ◽  
Vol 22 (1) ◽  
pp. 55-63 ◽  
Author(s):  
SHIH-FANG FAN ◽  
STEPHEN YAZULLA
Keyword(s):  
G Protein ◽  
Receptor Agonist ◽  
Lucifer Yellow ◽  
Reciprocal Inhibition ◽  
Receptor Activation ◽  
Light Signal ◽  
Bipolar Cells ◽  
Protein G ◽  
Calcium Dependent ◽  
Voltage Dependent

Cannabinoid CB1receptor (viaGs) and dopamine D2receptor (viaGi/o) antagonistically modulate goldfish cone membrane currents. As ON bipolar cells have CB1and D1receptors, but not D2receptors, we focused on whether CB1receptor agonist and dopamine interact to modulate voltage-dependent outward membrane K+currentsIK(V)of the ON mixed rod/cone (Mb) bipolar cells. Whole-cell currents were recorded from Mb bipolar cells in goldfish retinal slices. Mb bipolar cells were identified by intracellular filling with Lucifer yellow. The bath solution was calcium-free and contained 1 mM cobalt to block indirect calcium-dependent effects. Dopamine (10 μM) consistently increasedIK(V)by a factor of 1.57 ± 0.12 (S.E.M.,n= 15). A CB receptor agonist, WIN 55212-2 (0.25–1 μM), had no effect, but 4 μM WIN 55212-2 suppressedIK(V)by 60%. IfIK(V)was first increased by 10 μM dopamine, application of WIN 55212-2 (0.25–1 μM) reversibly blocked the effect of dopamine even though these concentrations of WIN 55212-2 had no effect of their own. If WIN 55212-2 was applied first and dopamine (10 μM) was added to the WIN-containing solution, 0.1 μM WIN 55212-2 blocked the effect of dopamine. All effects of WIN 55212-2 were blocked by coapplication of SR 141716A (CB1antagonist) and pretreatment with pertussis toxin (blocker of Gi/o) indicating actionviaCB1receptor activation of G protein Gi/o. Coactivation of CB1and D1receptors on Mb bipolar cells produces reciprocal effects onIK(V). The CB1-evoked suppression ofIK(V)is mediated by G protein Gi/o, whereas the D1-evoked enhancement is mediated by G protein Gs. As dopamine is a retinal “light” signal, these data support our notion that endocannabinoids function as a “dark” signal, interacting with dopamine to set retinal sensitivity.

scholarly journals Intracellular Na+inhibits voltage-dependent N-type Ca2+channels by a G protein βγ subunit-dependent mechanism

2004 ◽  
Vol 556 (1) ◽  
pp. 121-134 ◽  
Author(s):  
Yakov Blumenstein ◽  
Olexandr P. Maximyuk ◽  
Natalia Lozovaya ◽  
Natalia M. Yatsenko ◽  
Nataly Kanevsky ◽  
...  
Keyword(s):  
G Protein ◽  
Voltage Dependent ◽  
Ca2 Channels ◽  
Dependent Mechanism
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