scholarly journals Inhibitory Effect of Lomerizine, a Diphenylpiperazine Ca2+-Channel Blocker, on Ba2+ Current through Voltage-Gated Ca2+ Channels in PC12 Cells.

1997 ◽  
Vol 75 (2) ◽  
pp. 209-213 ◽  
Author(s):  
Tomokazu Watano ◽  
Hideaki Hara ◽  
Takayuki Sukamoto
Keyword(s):  
Pc12 Cells ◽  
Channel Blocker ◽  
Inhibitory Effect ◽  
Voltage Gated ◽  
Ca2 Channels

Nitric oxide suppresses vascular voltage-gated T-type Ca2+ channels through cGMP/PKG signaling

2014 ◽  
Vol 306 (2) ◽  
pp. H279-H285 ◽  
Author(s):  
Osama F. Harraz ◽  
Suzanne E. Brett ◽  
Donald G. Welsh
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Channel Blocker ◽  
Inhibitory Effect ◽  
No Donors ◽  
Channel Current ◽  
Steady State Inactivation ◽  
Arterial Smooth Muscle Cells ◽  
Patch Clamp Electrophysiology ◽  
Ca2 Channels

Recent reports have noted that T-type Ca2+ channels (CaV3.x) are expressed in vascular smooth muscle and are potential targets of regulation. In this study, we examined whether and by what mechanism nitric oxide (NO), a key vasodilator, influences this conductance. Using patch-clamp electrophysiology and rat cerebral arterial smooth muscle cells, we monitored an inward Ba2+ current that was divisible into a nifedipine-sensitive and -insensitive component. The latter was abolished by T-type channel blocker and displayed classic T-type properties including faster activation and steady-state inactivation at hyperpolarized potentials. NO donors (sodium nitroprusside, S-nitroso- N-acetyl- dl-penicillamine), along with activators of protein kinase G (PKG) signaling, suppressed T-type currents. Inhibitors of guanylyl cyclase/PKG {1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and KT5823, respectively}, had no effect on basal currents; KT5823 did, however, mask T-type Ca2+ channel current inhibition by NO/PKG. Functional experiments confirmed an inhibitory effect for NO on the T-type contribution to cerebral arterial myogenic tone. Cumulatively, our findings support the view that T-type Ca2+ channels are a regulatory target of vasodilatory signaling pathways. This targeting will influence Ca2+ dynamics and consequent tone development in the cerebral circulation.

scholarly journals Effects of Voltage-Gated K+Channel on Cell Proliferation in Multiple Myeloma

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Wei Wang ◽  
Yuying Fan ◽  
Shuye Wang ◽  
Lianjie Wang ◽  
Wanting He ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Multiple Myeloma ◽  
Cell Proliferation ◽  
Mtt Assay ◽  
Culture Medium ◽  
Channel Blocker ◽  
Inhibitory Effect ◽  
Resting Potential ◽  
Voltage Gated ◽  
Rpmi 8226

Objective. To study the effects and underlying mechanisms of voltage-gated K+channels on the proliferation of multiple myeloma cells.Methods. RPMI-8226 MM cell line was used for the experiments. Voltage-gated K+currents and the resting potential were recorded by whole-cell patch-clamp technique. RT-PCR detected Kv channel mRNA expression. Cell viability was analyzed with MTT assay. Cell counting system was employed to monitor cell proliferation. DNA contents and cell volume were analyzed by flow cytometry.Results. Currents recorded in RPMI-8226 cells were confirmed to be voltage-gated K+channels. A high level of Kv1.3 mRNA was detected but no Kv3.1 mRNA was detected in RPMI-8226 cells. Voltage-gated K+channel blocker 4-aminopyridine (4-AP) (2 mM) depolarized the resting potential from −42 ± 1.7 mV to −31.8 ± 2.8 mV(P<0.01). The results of MTT assay showed that there was no significant cytotoxicity to RPMI-8226 cells when the 4-AP concentration was lower than 4 mM. 4-AP arrested cell cycle in G0/G1 phase. Cells were synchronized at the G1/S boundary by treatment of aphidicolin and released from the blockage by replacing the medium with normal culture medium or with culture medium containing 2 mM 4-AP. 4-AP produced no significant inhibitory effect on cell cycle compared with control cells(P>0.05).Conclusions. In RPMI-8226, voltage-gated K+channels are involved in proliferation and cell cycle progression its influence on the resting potential and cell volume may be responsible for this process; the inhibitory effect of the voltage-gated K+channel blocker on RPMI-8226 cell proliferation is a phase-specific event.

Autoinhibition of transmitter release from PC12 cells and sympathetic neurons through a P2Y12 receptor-mediated inhibition of voltage-gated Ca2+ channels

2004 ◽  
Vol 20 (11) ◽  
pp. 2917-2928 ◽  
Author(s):  
Stefan G. Lechner ◽  
Mario M. Dorostkar ◽  
Martina Mayer ◽  
Hannah Edelbauer ◽  
Halyna Pankevych ◽  
...  
Keyword(s):  
Pc12 Cells ◽  
Transmitter Release ◽  
Sympathetic Neurons ◽  
P2y12 Receptor ◽  
Voltage Gated ◽  
Ca2 Channels

scholarly journals Pharmacological Dissection of the Crosstalk between NaV and CaV Channels in GH3b6 Cells

2022 ◽  
Vol 23 (2) ◽  
pp. 827
Author(s):  
Léa Réthoré ◽  
Joohee Park ◽  
Jérôme Montnach ◽  
Sébastien Nicolas ◽  
Joseph Khoury ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Channel Blocker ◽  
Excitable Cells ◽  
Voltage Gated ◽  
Na Currents ◽  
Rat Pituitary ◽  
Nav Channels ◽  
The Impact ◽  
Insight Into ◽  
Ca2 Channels

Thanks to the crosstalk between Na+ and Ca2+ channels, Na+ and Ca2+ homeostasis interplay in so-called excitable cells enables the generation of action potential in response to electrical stimulation. Here, we investigated the impact of persistent activation of voltage-gated Na+ (NaV) channels by neurotoxins, such as veratridine (VTD), on intracellular Ca2+ concentration ([Ca2+]i) in a model of excitable cells, the rat pituitary GH3b6 cells, in order to identify the molecular actors involved in Na+-Ca2+ homeostasis crosstalk. By combining RT-qPCR, immunoblotting, immunocytochemistry, and patch-clamp techniques, we showed that GH3b6 cells predominantly express the NaV1.3 channel subtype, which likely endorses their voltage-activated Na+ currents. Notably, these Na+ currents were blocked by ICA-121431 and activated by the β-scorpion toxin Tf2, two selective NaV1.3 channel ligands. Using Fura-2, we showed that VTD induced a [Ca2+]i increase. This effect was suppressed by the selective NaV channel blocker tetrodotoxin, as well by the selective L-type CaV channel (LTCC) blocker nifedipine. We also evidenced that crobenetine, a NaV channel blocker, abolished VTD-induced [Ca2+]i elevation, while it had no effects on LTCC. Altogether, our findings highlight a crosstalk between NaV and LTCC in GH3b6 cells, providing a new insight into the mode of action of neurotoxins.

Ca2+ Channel Antagonist U-92032 Inhibits Both T-Type Ca2+ Channels and Na+ Channels in Hippocampal CA1 Pyramidal Neurons

1997 ◽  
Vol 77 (2) ◽  
pp. 1023-1028 ◽  
Author(s):  
Robert B. Avery ◽  
Daniel Johnston
Keyword(s):  
Pyramidal Neurons ◽  
Channel Blocker ◽  
Cell Voltage ◽  
Ionic Currents ◽  
Hippocampal Pyramidal Neurons ◽  
Voltage Gated ◽  
Ca1 Pyramidal Neurons ◽  
Hippocampal Ca1 ◽  
Old Rats ◽  
Ca2 Channels

Avery, Robert B. and Daniel Johnston. Ca2+ channel antagonist U-92032 inhibits both T-type Ca2+ channels and Na+ channels in hippocampal CA1 pyramidal neurons. J. Neurophysiol. 77: 1023–1028, 1997. The effects of 7-[[4-[bis(4-fluoropheny l ) - m e t h y l ] - 1 - p i p e r a z i n y l ] m e t h y l ] - 2 - [ ( 2 - h y d r o x y e t h y l ) a m i n o ]4 -( 1 - m e t h y l e t h y l ) - 2 , 4 , 6 - c y c l o h e p t a t r i e n - 1 - o n e  ( U - 9 2 0 3 2 ) ,  anewly described Ca2+ channel blocker, on voltage-gated ionic currents were measured. Whole cell voltage-clamp records were obtained from acutely isolated CA1 hippocampal pyramidal neurons from 7- to 14-day-old rats. Dimethyl sulfoxide, at either 0.01% or 0.1%, partially inhibited T-type Ca2+ currents (∼20% inhibition) but not high-voltage-activated (HVA) Ca2+ currents. Ethanol (0.2%) did not affect Ca2+ currents. U-92032 selectively inhibited T-type Ca2+ currents (median inhibiting concentration ∼ 500 nM). HVA Ca2+ currents were less sensitive, with ∼75% of the current resistant at 10 μM. Inhibition of Ca2+ currents was reversible. U-92032 inhibited Na+ currents at concentrations similar to those required for T-type currents (>33% block at 1 μM). Block of Na+ currents took several minutes to develop and was irreversible. Voltage-gated K+ currents were insensitive to U-92032 (1 or 10 μM). These results indicate that U-92032 inhibits both T-type Ca2+ channels and Na+ channels, constraining its utility in certain studies. Among Ca2+ channels, however, U-92032 should prove a useful tool for distinguishing physiological contributions of T-type channels.

Roles of Ca2+ influx through ATP-activated channels in catecholamine release from pheochromocytoma PC12 cells

1992 ◽  
Vol 68 (6) ◽  
pp. 2026-2032 ◽  
Author(s):  
K. Nakazawa ◽  
K. Inoue
Keyword(s):  
Pc12 Cells ◽  
Dopamine Release ◽  
Cell Voltage ◽  
Catecholamine Release ◽  
K Channel ◽  
Voltage Gated ◽  
Inward Currents ◽  
Pheochromocytoma Pc12 ◽  
Pheochromocytoma Pc12 Cells ◽  
Ca2 Channels

1. Extracellular ATP evokes catecholamine release concomitant with depolarization in pheochromocytoma PC12 cells. Roles of Ca2+ influx through ATP-activated channels during the catecholamine release were investigated. 2. Norepinephrine or dopamine release induced by > or = 100-microM concentrations of ATP was insensitive to 300 microM Cd2+, whereas the release induced by increasing extracellular KCl (50-150 mM) was completely blocked by this concentration of Cd2+. 3. ATP (100 microM) increased the intracellular free Ca2+ concentration measured with fura-2. The increase was not affected by 300 microM Cd2+ or 100 microM nicardipine, suggesting that Ca2+ influx through ATP-activated channels but not through voltage-gated Ca2+ channels contributes to the ATP-evoked catecholamine release. 4. Inward currents permeating through voltage-gated Ca2+ channels were measured using the whole-cell voltage clamp. In the presence of 10 microM ATP, a concentration that induces an ATP-activated channel-mediated current equivalent to that induced by 100 microM ATP during the depolarization in "non-voltage clamped" cells, the Ca2+ current activated by a voltage step to +10 mV was reduced. The reduction in the Ca2+ channel-mediated current was not observed when the extracellular Ca2+ was replaced with Ba2+. 5. The ATP (100 microM)-evoked dopamine release was inhibited by 300 microM Cd2+ when measured with extracellular Ba2+ instead of Ca2+. This effect of Ba2+ may not be related to K+ channel-blocking activity, because the ATP-evoked dopamine release obtained with 5 mM tetraethylammonium (TEA) was not inhibited by Cd2+.(ABSTRACT TRUNCATED AT 250 WORDS)

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