Differential effect of desipramine and 2-hydroxydesipramine on depolarization-induced calcium uptake in synaptosomes from rat limbic sites

1995 ◽  
Vol 73 (5) ◽  
pp. 619-623 ◽  
Author(s):  
G. Beauchamp ◽  
P.-A. Lavoie ◽  
R. Elie
Keyword(s):  
Calcium Channel ◽  
Plasma Concentrations ◽  
Cingulate Cortex ◽  
Clinical Activity ◽  
Ca Uptake ◽  
Voltage Dependent ◽  
Dependent Inhibition ◽  
Voltage Dependent Calcium Channels ◽  
A Minor ◽  
The Brain

This study was conducted to investigate the inhibition of synaptosomal 45Ca uptake by desipramine and its major metabolite 2-hydroxydesipramine in the rat hippocampus and cingulate cortex, areas associated with emotional control. A concentration-dependent inhibition of net depolarization-induced 45Ca uptake was observed for desipramine (20–200 μM) in synaptosomes from both sites. However, 20 μM 2-hydroxydesipramine failed to inhibit calcium channel function in either of the two limbic sites; higher concentrations (60 or 200 μM) did produce a minor degree of inhibition in hippocampus synaptosomes. Others have shown that the clinically encountered plasma concentrations of 2-hydroxydesipramine are lower than those of desipramine, and the brain concentration of 2-hydroxydesipramine is therefore not expected to surpass or even reach 20 μM. In view of the previously observed clinical activity of 2-hydroxydesipramine, the present results indicate that calcium channel antagonism may not be the basis for the therapeutic effect of tricyclic antidepressants.Key words: voltage-dependent calcium channels, 45Ca uptake, hippocampus, cingulate cortex, tricyclic antidepressants.

scholarly journals Voltage-Dependent Calcium Channel CaV1.3 Subunits Regulate the Light Peak of the Electroretinogram

2007 ◽  
Vol 97 (5) ◽  
pp. 3731-3735 ◽  
Author(s):  
Jiang Wu ◽  
Alan D. Marmorstein ◽  
Jörg Striessnig ◽  
Neal S. Peachey
Keyword(s):  
Calcium Channel ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Rod Photoreceptor ◽  
Wild Type ◽  
Fast Oscillation ◽  
Light Peak ◽  
Voltage Dependent Calcium Channel ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels

In response to light, the mouse retinal pigment epithelium (RPE) generates a series of slow changes in potential that are referred to as the c-wave, fast oscillation (FO), and light peak (LP) of the electroretinogram (ERG). The LP is generated by a depolarization of the basolateral RPE plasma membrane by the activation of a calcium-sensitive chloride conductance. We have previously shown that the LP is reduced in both mice and rats by nimodipine, which blocks voltage-dependent calcium channels (VDCCs) and is abnormal in lethargic mice, carrying a null mutation in the calcium channel β4 subunit. To define the α1 subunit involved in this process, we examined mice lacking CaV1.3. In comparison with wild-type (WT) control littermates, LPs were reduced in CaV1.3−/− mice. This pattern matched closely with that previously noted in lethargic mice, confirming a role for VDCCs in regulating the signaling pathway that culminates in LP generation. These abnormalities do not reflect a defect in rod photoreceptor activity, which provides the input to the RPE to generate the c-wave, FO, and LP, because ERG a-waves were comparable in WT and CaV1.3−/− littermates. Our results identify CaV1.3 as the principal pore-forming subunit of VDCCs involved in stimulating the ERG LP.

scholarly journals Comparison of the effects of L-type calcium channel antagonist Amlodipine with L/N-type calcium channel antagonist Cilnidipine on blood pressure, heart rate, proteinuria and lipid profile in hypertensive patients

2016 ◽  
Vol 15 (3) ◽  
pp. 460-465
Author(s):  
Kiran Kumar Singal ◽  
Neerja Singal ◽  
Abhinav Gupta ◽  
Akash Garg ◽  
Ravi Kumar
Keyword(s):  
Blood Pressure ◽  
Calcium Channel ◽  
Calcium Channel Antagonist ◽  
Total Cholesterol Level ◽  
Medical Science ◽  
Reflex Tachycardia ◽  
Before And After ◽  
Voltage Dependent ◽  
Amlodipine Group ◽  
Voltage Dependent Calcium Channels

Background: Cilnidipine is a novel and unique 1,4-dydropyridine derivative calcium antagonist that exerts potent inhibitory actions not only on L-type but also on N-type voltage dependent calcium channels. Blockade of the neural N-type calcium channel inhibits the secretion of norepinephrine from peripheral neural terminals and depresses sympathetic nervous system activity.Objective and methods: The purpose of this study was to assess the effect of Cilnidipine and Amlodipine on blood pressure (BP) levels. We did BP monitoring before and after once-daily use of Cilnidipine and Amlodipine in 100 hypertensive patients.Results: Both drugs significantly reduced systolic BP (SBP) and diastolic BP (DBP). However, the reductions in pulse rate (PR) were significantly greater in the Cilnidipine group than the Amlodipine group. N-type calcium channel blockade by Cilnidipine may not cause reflex tachycardia, and may be useful for hypertensive treatment.Conclusion: There was significant reduction in proteinuria with Clindipine as compared to Amlodipine. However, there were no significant change in total cholesterol level in diabetes and non-diabetics in both the group.Bangladesh Journal of Medical Science Vol.15(3) 2016 p.460-465

scholarly journals Chemical Analysis and Calcium Channel Blocking Activity of the Essential Oil of Perovskia abrotanoides

2013 ◽  
Vol 8 (11) ◽  
pp. 1934578X1300801 ◽  
Author(s):  
Abdul Jabbar Shah ◽  
Munawwer Rasheed ◽  
Qaiser Jabeen ◽  
Amir Ahmed ◽  
Rasool Bakhsh Tareen ◽  
...  
Keyword(s):  
Essential Oil ◽  
Calcium Channel ◽  
Response Curves ◽  
Spasmolytic Activity ◽  
Medicinal Use ◽  
Voltage Dependent ◽  
Rabbit Jejunum ◽  
Voltage Dependent Calcium Channels ◽  
Pre Treatment ◽  
Perovskia Abrotanoides

The aim of this study was to investigate the chemical composition and provide a pharmacological base for the medicinal use of the essential oil of Perovskia abrotanoides (Pa. Oil) in gastrointestinal disorders, such as colic. The chemical investigation resulted in the identification of 26 compounds, of which tricyclene, β- trans-ocimene, terpinene-4-acetate, terpinen-4-ol, caran-3β-ol, linalyl acetate, β-caryophyllene oxide and α-elemene had not previously been reported from P. abrotanoides. Major constituents were 1,8-cineol and δ–3-carene, which constituting 50% of the oil. In the isolated rabbit jejunum preparation Pa.Oil caused inhibition of spontaneous and high K+ (80 mM)-induced contractions, with respective EC50 values of 0.13 (0.08-0.20; n=4) and 0.90 mg/mL (0.50–1.60; n=5), thus showing that spasmolytic activity is mediated possibly through calcium channel blockade (CCB). The CCB activity was confirmed when pre-treatment of the tissue with Pa. Oil (0.03-0.1 mg/mL) caused a rightward shift in the Ca++ concentration-response curves, similar to that caused by verapamil, a standard calcium channel blocker. These data indicate that the essential oil of P. abrotanoides possesses spasmolytic activity mediated possibly through inhibition of voltage-dependent calcium channels, which may explain its medicinal use in colic and possibly diarrhea.

Calcium channels contribute to the decrease in blood pressure of pregnant rats

2002 ◽  
Vol 282 (2) ◽  
pp. H665-H671 ◽  
Author(s):  
May Simaan ◽  
Chanterelle Cadorette ◽  
Matthieu Poterek ◽  
Jean St-Louis ◽  
Michèle Brochu
Keyword(s):  
Blood Pressure ◽  
Calcium Channels ◽  
Calcium Channel ◽  
Plasma Renin ◽  
Late Pregnancy ◽  
Pregnant Rats ◽  
Affect Body Weight ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels ◽  
Calcium Channel Activator

Pregnancy is associated with hemodynamic changes such as reduced vascular resistance and blood pressure. We reported that, during late pregnancy, the activity of voltage-dependent calcium channels (VDCC) is altered in the adrenal cortex and vascular smooth muscle. These observations suggested that the late pregnancy-induced decrease in blood pressure is linked to diminished VDCC function. We attempted to prevent pregnancy-induced reduced blood pressure with a calcium channel activator (CGP 28392) in pregnant rats and to mimic it by administration of a calcium channel blocker (nifedipine) to nonpregnant rats. Treatment was given from the 15th day of gestation for 7 days. The systolic blood pressure of CGP 28392-treated pregnant rats rose transiently for 2 days and then declined toward values of nontreated pregnant controls, although remaining higher. However, nonpregnant rats maintained their high arterial pressure throughout CGP 28392 treatment. Nifedipine lowered the blood pressure in nonpregnant rats to values of nontreated term-pregnant controls. Both agents did not affect body weight, water or food intake, plasma renin activity, and plasma aldosterone or corticosterone levels. Nifedipine and CGP 28392 treatment of nonpregnant and pregnant animals, respectively, did not modify the response of aortic rings to KCl. These results show that VDCC activation caused hypertension, which modified the extent of the decrease in blood pressure at the end of pregnancy.

Dihydropyridine-sensitive single calcium channels in airway smooth muscle cells

1990 ◽  
Vol 259 (6) ◽  
pp. L468-L480 ◽  
Author(s):  
J. F. Worley ◽  
M. I. Kotlikoff
Keyword(s):  
Smooth Muscle ◽  
Calcium Channels ◽  
Smooth Muscle Cells ◽  
Calcium Channel ◽  
Airway Smooth Muscle ◽  
Muscle Cells ◽  
Membrane Depolarization ◽  
Airway Smooth Muscle Cells ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels

We have identified and characterized single voltage-dependent calcium channels in both acutely dissociated rat bronchial and cultured human tracheobronchial smooth muscle cells using the patch-clamp technique. In both cell types, on-cell membrane patches displayed unitary currents selective for barium ions and exhibited one conductance level (21–26 pS), and the open state probability was increased by membrane depolarization. Unitary barium currents were enhanced by the calcium channel selective agonist, BAY R 5417, and inhibited by the dihydropyridine calcium channel antagonist, nisoldipine (apparent inhibition constant less than 100 nM). Moreover, the degree of nisoldipine inhibition of the rat bronchial smooth muscle channels was increased with membrane depolarization in a manner consistent with the drug interacting with highest affinity to the inactivated channel state. In addition, the sensitivity to BAY R 5417 augmentation and nisoldipine inhibition of depolarization-induced tonic force of intact rat bronchial ring segments was in close agreement to the single channel results. Thus these data suggest that activation of voltage-dependent calcium channels can influence airway contraction and that dihydropyridines may be effective modulators of depolarization-induced increases in bronchial tone. We conclude that both rat and human airway smooth muscle cells have high-conductance voltage-dependent calcium channels that interact in a predictable manner with dihydropyridines and are similar to voltage-dependent calcium channels observed in other smooth muscle cells.

Dissection of the Calcium Channel Domains Responsible for Modulation of Neuronal Voltage-Dependent Calcium Channels by G Proteins

1999 ◽  
Vol 868 (1 MOLECULAR AND) ◽  
pp. 160-174 ◽  
Author(s):  
ANNETTE C. DOLPHIN ◽  
KAREN M. PAGE ◽  
NICHOLAS S. BERROW ◽  
GARY J. STEPHENS ◽  
CARLES CANTI
Keyword(s):  
Calcium Channels ◽  
Calcium Channel ◽  
G Proteins ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels

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.

scholarly journals Partners in Crime: Towards New Ways of Targeting Calcium Channels

2019 ◽  
Vol 20 (24) ◽  
pp. 6344 ◽  
Author(s):  
Lucile Noyer ◽  
Loic Lemonnier ◽  
Pascal Mariot ◽  
Dimitra Gkika
Keyword(s):  
Calcium Channels ◽  
Calcium Channel ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Interaction Domain ◽  
Domain Structures ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels ◽  
Transient Receptor ◽  
Partner Proteins

The characterization of calcium channel interactome in the last decades opened a new way of perceiving ion channel function and regulation. Partner proteins of ion channels can now be considered as major components of the calcium homeostatic mechanisms, while the reinforcement or disruption of their interaction with the channel units now represents an attractive target in research and therapeutics. In this review we will focus on the targeting of calcium channel partner proteins in order to act on the channel activity, and on its consequences for cell and organism physiology. Given the recent advances in the partner proteins’ identification, characterization, as well as in the resolution of their interaction domain structures, we will develop the latest findings on the interacting proteins of the following channels: voltage-dependent calcium channels, transient receptor potential and ORAI channels, and inositol 1,4,5-trisphosphate receptor.

Pavlovian eyeblink conditioning is severely impaired in tottering mice

2020 ◽  
Author(s):  
Nina L. de Oude ◽  
Freek E. Hoebeek ◽  
Michiel M. ten Brinke ◽  
Chris I. de Zeeuw ◽  
Henk-Jan Boele
Keyword(s):  
Neuronal Excitability ◽  
Eyeblink Conditioning ◽  
Learning Task ◽  
Loss Of Function ◽  
Oscillatory State ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels ◽  
Dependent Learning ◽  
The Brain ◽  
Normal Calcium

Cacna1a encodes the pore-forming α1A subunit of CaV2.1 voltage-dependent calcium channels, which regulate neuronal excitability and synaptic transmission. Purkinje cells in the cortex of cerebellum abundantly express these CaV2.1 channels. Here, we show that homozygous tottering (tg) mice, which carry a loss-of-function Cacna1a mutation, exhibit severely impaired learning in Pavlovian eyeblink conditioning, which is a cerebellar dependent learning task. Performance of reflexive eyeblinks is unaffected in tg mice. Transient seizure activity in tg mice further corrupted the amplitude of eyeblink CRs. Our results indicate that normal calcium homeostasis is imperative for cerebellar learning and that the oscillatory state of the brain can affect the expression thereof.

Molecular characterization of renal calcium channel beta-subunit transcripts

1995 ◽  
Vol 268 (3) ◽  
pp. F525-F531 ◽  
Author(s):  
A. S. Yu ◽  
M. Boim ◽  
S. C. Hebert ◽  
A. Castellano ◽  
E. Perez-Reyes ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Calcium Channel ◽  
Rat Kidney ◽  
Beta Subunit ◽  
Kidney Cortex ◽  
Calcium Excretion ◽  
Gene Transcript ◽  
Degenerate Primers ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels

An apical, hormone-regulated, calcium entry channel in the distal convoluted tubule and/or connecting tubule (DCT/CNT) is thought to play an important role in controlling renal calcium excretion. We previously identified a gene transcript encoding the pore-forming alpha 1-subunit of a calcium channel (alpha 1A, or CaCh4) which may be a candidate for such a molecule. The properties of voltage-dependent calcium channels are known to be modulated by their beta-subunits. To identify the accessory beta-subunit of DCT/CNT calcium channels, degenerate primers based on published beta-subunit sequences were used to amplify rat kidney cDNA by the polymerase chain reaction (PCR), and the products were subcloned and sequenced. Alternatively spliced transcripts of three beta-subunit genes (beta 2, beta 3, and beta 4) were identified. Northern blot analysis indicated that beta 4-subunit is preferentially expressed in kidney cortex. Transcripts of all three beta-subunit genes were detected by PCR in microdissected nephron segments, but only beta 4-subunit was found in DCT/CNT. As the beta 4- and alpha 1A-subunits colocalize to the DCT/CNT, we hypothesize that they may be constituent subunits of a renal calcium channel regulated by a hormone(s).

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