scholarly journals Is there a role for T-type Ca2+ channels in regulation of vasomotor tone in mesenteric arterioles?This article is part of a Special Issue on Information Transfer in the Microcirculation.

2009 ◽  
Vol 87 (1) ◽  
pp. 8-20 ◽  
Author(s):  
Lars Jørn Jensen ◽  
Niels-Henrik Holstein-Rathlou
Keyword(s):  
Information Transfer ◽  
Electromechanical Coupling ◽  
Low Voltage ◽  
Vasomotor Tone ◽  
Direct Demonstration ◽  
Voltage Dependent ◽  
Small Conductance ◽  
Ca2 Channels ◽  
Peripheral Blood Pressure

The largest peripheral blood pressure drop occurs in terminal arterioles (<40 µm lumen diameter). L-type voltage-dependent Ca2+ channels (VDCCs) are considered the primary pathway for Ca2+ influx during physiologic activation of vascular smooth muscle cells (VSMC). Recent evidence suggests that T-type VDCCs are expressed in renal afferent and efferent arterioles, mesenteric arterioles, and skeletal muscle arterioles. T-type channels are small-conductance, low voltage-activated, fast-inactivating channels. Thus, their role in supplying Ca2+ for contraction of VSMC has been disputed. However, T-type channels display non-inactivating window currents, which may play a role in sustained Ca2+ entry. Here, we review the possible role of T-type channels in vasomotor tone regulation in rat mesenteric terminal arterioles. The CaV3.1 channel was immunolocalized in VSMC, whereas the CaV3.2 channel was predominantly expressed in endothelial cells. Voltage-dependent Ca2+ entry was inhibited by the new specific T-type blockers R(–)-efonidipine and NNC 55-0396. The effect of NNC 55-0396 persisted in depolarized arterioles, suggesting an unusually high activation threshold of mesenteric T-type channels. T-type channels were not necessary for conduction of vasoconstriction, but appear to be important for local electromechanical coupling in VSMC. The first direct demonstration of endothelial T-type channels warrants new investigations of their role in vascular biology.

Role of Ca2+ and Na+ on luteinizing hormone release from the calf pituitary

1988 ◽  
Vol 255 (4) ◽  
pp. E469-E474
Author(s):  
J. P. Kile ◽  
M. S. Amoss
Keyword(s):  
Luteinizing Hormone ◽  
Ionophore A23187 ◽  
Channel Blockers ◽  
Hormone Release ◽  
Primary Cells ◽  
Rat Pituitary ◽  
Voltage Dependent ◽  
Lh Release ◽  
Ca2 Channels

It has been proposed that gonadotropin-releasing hormone (GnRH) stimulates Ca2+ entry by activation of voltage-independent, receptor-mediated Ca2+ channels in the rat gonadotroph. Little work has been done on the role of calcium in GnRH-induced luteinizing hormone (LH) release in species other than the rat. Therefore, this study was done to compare the effects of agents that alter Ca2+ or Na+ entry on LH release from calf anterior pituitary primary cells in culture. GnRH (100 ng/ml), Ca2+ ionophore A23187 (2.5 microM), and the depolarizing agent ouabain (0.1-10 microM) all produced significant increases (P less than 0.05) in LH release; these effects were significantly reduced when the cells were preincubated with the organic Ca2+ channel blockers nifedipine (1-10 microM) and verapamil (1-10 microM) and with Co2+ (0.01-1 mM). The effect of ouabain was inhibited by tetrodotoxin (TTX; 1-10 nM) as well as by nifedipine at 0.1-10 microM. In contrast to its effect on rat pituitary LH release, TTX significantly inhibited GnRH-stimulated LH release at 1-100 nM. These results suggest that GnRH-induced LH release may employ Ca2+ as a second messenger in bovine gonadotrophs and support recent speculation that GnRH-induced Ca2+ mobilization may in part be voltage dependent.

scholarly journals Voltage-gated transient currents in bovine adrenal fasciculata cells. I. T-type Ca2+ current.

1993 ◽  
Vol 102 (2) ◽  
pp. 217-237 ◽  
Author(s):  
B Mlinar ◽  
B A Biagi ◽  
J J Enyeart
Keyword(s):  
Time Constant ◽  
Low Voltage ◽  
Zona Fasciculata ◽  
Patch Clamp Technique ◽  
Time Constants ◽  
Voltage Gated ◽  
Wide Range ◽  
Boltzmann Function ◽  
Voltage Dependent ◽  
Ca2 Channels

The whole cell version of the patch clamp technique was used to identify and characterize voltage-gated Ca2+ channels in enzymatically dissociated bovine adrenal zona fasciculata (AZF) cells. The great majority of cells (84 of 86) expressed only low voltage-activated, rapidly inactivating Ca2+ current with properties of T-type Ca2+ current described in other cells. Voltage-dependent activation of this current was fit by a Boltzmann function raised to an integer power of 4 with a midpoint at -17 mV. Independent estimates of the single channel gating charge obtained from the activation curve and using the "limiting logarithmic potential sensitivity" were 8.1 and 6.8 elementary charges, respectively. Inactivation was a steep function of voltage with a v1/2 of -49.9 mV and a slope factor K of 3.73 mV. The expression of a single Ca2+ channel subtype by AZF cells allowed the voltage-dependent gating and kinetic properties of T current to be studied over a wide range of potentials. Analysis of the gating kinetics of this Ca2+ current indicate that T channel activation, inactivation, deactivation (closing), and reactivation (recovery from inactivation) each include voltage-independent transitions that become rate limiting at extreme voltages. Ca2+ current activated with voltage-dependent sigmoidal kinetics that were described by an m4 model. The activation time constant varied exponentially at test potentials between -30 and +10 mV, approaching a voltage-independent minimum of 1.6 ms. The inactivation time constant (tau i) also decreased exponentially to a minimum of 18.3 ms at potentials positive to 0 mV. T channel closing (deactivation) was faster at more negative voltages; the deactivation time constant (tau d) decreased from 8.14 +/- 0.7 to 0.48 +/- 0.1 ms at potentials between -40 and -150 mV. T channels inactivated by depolarization returned to the closed state along pathways that included two voltage-dependent time constants. tau rec-s ranged from 8.11 to 4.80 s when the recovery potential was varied from -50 to -90 mV, while tau rec-f decreased from 1.01 to 0.372 s. At potentials negative to -70 mV, both time constants approached minimum values. The low voltage-activated Ca2+ current in AZF cells was blocked by the T channel selective antagonist Ni2+ with an IC50 of 20 microM. At similar concentrations, Ni2+ also blocked cortisol secretion stimulated by adrenocorticotropic hormone. Our results indicate that bovine AZF cells are distinctive among secretory cells in expressing primarily or exclusively T-type Ca2+ channels.(ABSTRACT TRUNCATED AT 400 WORDS)

Role of K+ channels in adrenal catecholamine secretion in anesthetized dogs

1998 ◽  
Vol 274 (4) ◽  
pp. R1125-R1130 ◽  
Author(s):  
Takahiro Nagayama ◽  
Kimiya Masada ◽  
Makoto Yoshida ◽  
Mizue Suzuki-Kusaba ◽  
Hiroaki Hisa ◽  
...  
Keyword(s):  
Channel Blocker ◽  
Splanchnic Nerve ◽  
Channel Blockers ◽  
Cholinergic Agonists ◽  
Voltage Dependent ◽  
Anesthetized Dogs ◽  
Splanchnic Nerve Stimulation ◽  
Mast Cell Degranulating ◽  
Small Conductance

We examined the role of K+ channels in the secretion of adrenal catecholamine (CA) in response to splanchnic nerve stimulation (SNS), acetylcholine (ACh), 1,1-dimethyl-4-phenyl-piperazinium (DMPP), and muscarine in anesthetized dogs. K+ channel blockers and the cholinergic agonists were infused and injected, respectively, into the adrenal gland. The voltage-dependent K+ channel (KA type) blocker mast cell degranulating (MCD) peptide infusion (10–100 ng/min) enhanced increases in CA output induced by SNS (1–3 Hz), but it did not affect increases in CA output induced by ACh (0.75–3 μg), DMPP (0.1–0.4 μg), or muscarine (0.5–2 μg). The small-conductance Ca2+-activated K+(SKCa) channel blocker scyllatoxin infusion (10–100 ng/min) enhanced the ACh-, DMPP-, and muscarine-induced increases in CA output, but it did not affect the SNS-induced increases in CA output. These results suggest that KA channels may play an inhibitory role in the regulation of adrenal CA secretion in response to SNS and that SKCa channels may play the same role in the secretion in response to exogenously applied cholinergic agonists.

Modulation of voltage-dependent Ca2+ conductance by changing Cl- concentration in rat lactotrophs

1997 ◽  
Vol 272 (4) ◽  
pp. C1178-C1185 ◽  
Author(s):  
L. Garcia ◽  
M. Fahmi ◽  
N. Prevarskaya ◽  
B. Dufy ◽  
P. Sartor
Keyword(s):  
Carboxylic Acid ◽  
Fluorescence Probe ◽  
Physiological Role ◽  
Feedback Mechanism ◽  
Pituitary Cells ◽  
Physiological Processes ◽  
Voltage Dependent ◽  
Ca2 Channels ◽  
Cl Conductance

In pituitary cells, voltage-dependent Ca2+ channels play an important role in such physiological processes as exocytosis, secretion, the cell cycle, and proliferation. Thus mechanisms that modulate voltage-dependent Ca2+ channel activity participate indirectly in regulating intracellular Ca2+ concentration. We have shown a new modulating mechanism for voltage-dependent Ca2+ channels by demonstrating that Ca2+ influx is influenced by Cl-. To evaluate the role of Cl- on Ca2+ conductance coupling, we first measured the intracellular Cl- concentration of rat lactotrophs using the Cl(-)-sensitive fluorescence probe sulfopropylquinolinium by simple microspectrofluorometry or combined with electrophysiology. We found an average intracellular Cl- concentration of rat lactotrophs of approximately 60 mM (n = 39). Using the whole cell tight-seal recording technique, we showed that a reduction in external Cl- concentration ([Cl-]o) and a decrease in Cl- conductances affected Ca2+ conductance as measured by Ba2+ movement through the Ca2+ channels (I(Ba)). Low [Cl-]o (39 mM) induced a decrease in Ca2+ entry via voltage-gated Ca2+ channels (-27.75 +/- 4% of normalized I(Ba)). Similarly, blockade of the Cl- conductance by 1 mM 9-anthracene carboxylic acid induced a decrease in I(Ba) (-26 +/- 6% of normalized I(Ba)). This modulation of I(Ba) was inhibited by 24-h pretreatment of the cells with pertussis toxin (1 microg/ml), suggesting that changes in Cl- concentration induced by low [Cl-]o and 9-anthracene carboxylic acid interfered with the phosphorylation of G proteins involved in Ca2+ channel activation. These results suggest a feedback mechanism based on constant interaction between Ca2+ and Cl-. Finally, they also emphasize the physiological role of Cl- in rat lactotrophs.

scholarly journals Voltage-gated calcium channels in GtoPdb v.2021.2

2021 ◽  
Vol 2021 (2) ◽  
Author(s):  
William A. Catterall ◽  
Edward Perez-Reyes ◽  
Terrance P. Snutch ◽  
Jörg Striessnig
Keyword(s):  
High Voltage ◽  
Low Voltage ◽  
Transmembrane Domains ◽  
Voltage Gated ◽  
Voltage Dependent ◽  
Alternatively Spliced ◽  
Membrane Spanning ◽  
Voltage Gated Ion Channels ◽  
Ca2 Channels ◽  
Α1 Subunit

Calcium (Ca2+) channels are voltage-gated ion channels present in the membrane of most excitable cells. The nomenclature for Ca2+channels was proposed by [127] and approved by the NC-IUPHAR Subcommittee on Ca2+ channels [70]. Most Ca2+ channels form hetero-oligomeric complexes. The α1 subunit is pore-forming and provides the binding site(s) for practically all agonists and antagonists. The 10 cloned α1-subunits can be grouped into three families: (1) the high-voltage activated dihydropyridine-sensitive (L-type, CaV1.x) channels; (2) the high- to moderate-voltage activated dihydropyridine-insensitive (CaV2.x) channels and (3) the low-voltage-activated (T-type, CaV3.x) channels. Each α1 subunit has four homologous repeats (I-IV), each repeat having six transmembrane domains and a pore-forming region between transmembrane domains S5 and S6. Voltage-dependent gating is driven by the membrane spanning S4 segment, which contains highly conserved positive charges that respond to changes in membrane potential. All of the α1-subunit genes give rise to alternatively spliced products. At least for high-voltage activated channels, it is likely that native channels comprise co-assemblies of α1, β and α2-δ subunits. The γ subunits have not been proven to associate with channels other than the α1s skeletal muscle Cav1.1 channel. The α2-δ1 and α2-δ2 subunits bind gabapentin and pregabalin.

Characterizing voltage-dependent Ca2+ channels coupled to VIP release and NO synthesis in enteric synaptosomes

2002 ◽  
Vol 283 (5) ◽  
pp. G1027-G1034 ◽  
Author(s):  
M. Kurjak ◽  
A. Sennefelder ◽  
M. Aigner ◽  
V. Schusdziarra ◽  
H. D. Allescher
Keyword(s):  
Nitric Oxide ◽  
No Synthase ◽  
Channel Blockers ◽  
Voltage Dependent ◽  
Intracellular Ca ◽  
P Type ◽  
Ca2 Channels

In enteric synaptosomes of the rat, the role of voltage-dependent Ca2+channels in K+-induced VIP release and nitric oxide (NO) synthesis was investigated. Basal VIP release was 39 ± 4 pg/mg, and cofactor-substituted NO synthase activity was 7.0 ± 0.8 fmol · mg−1 · min−1. K+ depolarization (65 mM) stimulated VIP release Ca2+ dependently (basal, 100%; K+, 172.2 ± 16.2%; P < 0.05, n = 5). K+-stimulated VIP release was reduced by blockers of the P-type (ω-agatoxin-IVA, 3 × 10−8 M) and N-type (ω-conotoxin-GVIA, 10−6 M) Ca2+ channels by ∼50 and 25%, respectively, but not by blockers of the L-type (isradipine, 10−8 M), Q-type (ω-conotoxin-MVIIC, 10−6 M), or T-type (Ni2+, 10−6 M) Ca2+ channels. In contrast, NO synthesis was suppressed by ω-agatoxin-IVA, ω-conotoxin-GVIA, and isradipine by ∼79, 70, and 70%, respectively, whereas Ni2+ and ω-conotoxin-MVIIC had no effect. These findings are suggestive of a coupling of depolarization-induced VIP release primarily to the P- and N-type Ca2+ channels, whereas NO synthesis is presumably dependent on Ca2+ influx not only via the P- and N- but also via the L-type Ca2+ channel. In contrast, none of the Ca2+ channel blockers affected VIP release evoked by exogenous NO, suggesting that NO induces VIP secretion by a different mechanism, presumably involving intracellular Ca2+ stores.

Selective inhibition of glucose-stimulated insulin release by dantrolene

1982 ◽  
Vol 243 (1) ◽  
pp. E59-E67 ◽  
Author(s):  
D. Janjic ◽  
C. B. Wollheim ◽  
G. W. Sharp
Keyword(s):  
Insulin Release ◽  
Selective Inhibition ◽  
Calcium Stores ◽  
Dantrolene Sodium ◽  
Voltage Dependent ◽  
14Co2 Production ◽  
Stimulus Secretion Coupling ◽  
Primary Action ◽  
Ca2 Channels

Dantrolene sodium, which interferes with excitation-contraction coupling by inhibiting the Ca2+ release from sarcoplasmic reticulum in muscle, was used to investigate the role of stored calcium in the stimulation of insulin release by various secretagogues. Insulin release was measured simultaneously with 45Ca2+ uptake or 45Ca2+ efflux from isolated rat pancreatic islets. Glucose-stimulated insulin release was inhibited by dantrolene (10–100 microM) as was glyceraldehyde- or mannose-stimulated release. In contrast, dantrolene failed to inhibit insulin release stimulated by leucine, arginine, ouabain, potassium, or 3-isobutyl-1-methylxanthine. Although dantrolene lowered glucose-stimulated 45Ca2+ uptake, nonspecific blockade of voltage-dependent Ca2+ channels may not be a primary action of dantrolene because K+-stimulated 45Ca2+ uptake was not inhibited. Glucose utilization (3H2O formation) was unaffected by dantrolene, whereas glucose oxidation (14CO2 production) was decreased. In the absence of Ca2+, the glucose-inhibited 45Ca2+ efflux was unchanged. At normal Ca2+, dantrolene inhibited glucose-stimulated 45Ca2+ efflux and veratridine induced insulin release. This suggests an interference with mobilization of beta-cell calcium stores. The selective action of dantrolene on insulin release makes it an interesting tool for further studies on stimulus-secretion coupling.

Local Anesthetics Modulate Neuronal Calcium Signaling through Multiple Sites of Action

2003 ◽  
Vol 98 (5) ◽  
pp. 1139-1146 ◽  
Author(s):  
Fang Xu ◽  
Zayra Garavito-Aguilar ◽  
Esperanza Recio-Pinto ◽  
Jin Zhang ◽  
Thomas J. J. Blanck
Keyword(s):  
Local Anesthetics ◽  
K Channel ◽  
Na Channels ◽  
Channel Blockade ◽  
K Channels ◽  
Voltage Dependent ◽  
Sites Of Action ◽  
A Site ◽  
Ca2 Channels

Background Local anesthetics (LAs) are known to inhibit voltage-dependent Na+ channels, as well as K+ and Ca2+ channels, but with lower potency. Since cellular excitability and responsiveness are largely determined by intracellular Ca2+ availability, sites along the Ca2+ signaling pathways may be targets of LAs. This study was aimed to investigate the LA effects on depolarization and receptor-mediated intracellular Ca2+ changes and to examine the role of Na+ and K+ channels in such functional responses. Methods Effects of bupivacaine, ropivacaine, mepivacaine, and lidocaine (0.1-2.3 mm) on evoked [Ca2+](i) transients were investigated in neuronal SH-SY5Y cell suspensions using Fura-2 as the intracellular Ca2+ indicator. Potassium chloride (KCl, 100 mm) and carbachol (1 mm) were individually or sequentially applied to evoke increases in intracellular Ca2+. Coapplication of LA and Na+/K+ channel blockers was used to evaluate the role of Na+ and K+ channels in the LA effect on the evoked [Ca2+](i) transients. Results All four LAs concentration-dependently inhibited both KCl- and carbachol-evoked [Ca2+](i) transients with the potency order bupivacaine &gt; ropivacaine &gt; lidocaine &gt;/= mepivacaine. The carbachol-evoked [Ca2+](i) transients were more sensitive to LAs without than with a KCl prestimulation, whereas the LA-effect on the KCl-evoked [Ca2+](i) transients was not uniformly affected by a carbachol prestimulation. Na+ channel blockade did not alter the evoked [Ca2+](i) transients with or without a LA. In the absence of LA, K+ channel blockade increased the KCl-, but decreased the carbachol-evoked [Ca2+](i) transients. A coapplication of LA and K+ channel blocker resulted in larger inhibition of both KCl- and carbachol-evoked [Ca2+](i) transients than by LA alone. Conclusions Different and overlapping sites of action of LAs are involved in inhibiting the KCl- and carbachol-evoked [Ca2+](i) transients, including voltage-dependent Ca2+ channels, a site associated with the caffeine-sensitive Ca2+ store and a possible site associated with the IP(3)-sensitive Ca2+ store, and a site in the muscarinic pathway. K+ channels, but not Na+ channels, seem to modulate the evoked [Ca2+](i) transients, as well as the LA-effects on such responses.

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