scholarly journals Multiple voltage-dependent mechanisms potentiate calcium channel activity in hippocampal neurons

1996 ◽  
Vol 16 (3) ◽  
pp. 1072-1082 ◽  
Author(s):  
ET Kavalali ◽  
MR Plummer
Keyword(s):  
Calcium Channel ◽  
Hippocampal Neurons ◽  
Channel Activity ◽  
Voltage Dependent

Synexin: Molecular Mechanism of Calcium-Dependent Membrane Fusion and Voltage-Dependent Calcium-Channel Activity.

1991 ◽  
Vol 635 (1 Calcium Entry) ◽  
pp. 328-351 ◽  
Author(s):  
HARVEY B. POLLARD ◽  
EDUARDO ROJAS ◽  
RICHARD W. PASTOR ◽  
EDUARDO M. ROJAS ◽  
H. ROBERT GUY ◽  
...  
Keyword(s):  
Calcium Channel ◽  
Membrane Fusion ◽  
Molecular Mechanism ◽  
Channel Activity ◽  
Calcium Dependent ◽  
Voltage Dependent Calcium Channel ◽  
Voltage Dependent

ABNORMAL CALCIUM CHANNEL ACTIVITY OF THE HIPPOCAMPAL NEURONS IN SPONTANEOUSLY EPILEPTIC RAT (SER), A DOUBLE MUTANT.

1992 ◽  
Vol 15 ◽  
pp. 164B
Author(s):  
M. Sasa ◽  
K. Ishihara ◽  
T. Momlyama ◽  
H. Ujihara ◽  
T. Serikawa ◽  
...  
Keyword(s):  
Calcium Channel ◽  
Hippocampal Neurons ◽  
Double Mutant ◽  
Channel Activity

scholarly journals Identification of “on-off residues” in rat Cav1.2 α1C subunit channel using in silico analysis and docking simulation

2016 ◽  
Author(s):  
Alfonso Trezza ◽  
Andrea Bernini ◽  
Ottavia Spiga
Keyword(s):  
Calcium Channel ◽  
Mechanism Of Action ◽  
Binding Sites ◽  
Docking Simulation ◽  
Cardiac Contraction ◽  
Hydroxyl Groups ◽  
Channel Activity ◽  
Molecular Graphics ◽  
Ligand Interaction ◽  
Voltage Dependent

Introduction Voltage-dependent calcium channels (VSCC) is involved in important biological function as calcium ion transmembrane transport and cardiac contraction. VSCC is a multi-pass membrane protein, made up from α-1, α-2, β and δ subunits. α-1 subunit regulates the entry of ion calcium. Voltage-dependent L-type calcium channel subunit alpha-1C (Cav1.2 α1C subunit channel) is an isoform of VSCC, and is characterized from an high-voltage activation. Previous study have shown that class of molecules as benzothiazepines (Tikhonov D. et al, 2008), are able to block the alpha-1C subunit. Recent works have demonstrated that molecules belonged at the flavonoid class are able to inhibit or to raise channel activity (Saponara S. et al, 2011). In this work, we reported the sensing- residues that could play a key role in Cav1.2 α1C activity. Furthermore, we proposed a potential mechanism of action inside Cav1.2 α1C binding-site with differences between inhibitors and stimulants. Our work has clarifiedas the ligands operate on Cav1.2 α1C, this information could be useful in order to improve their usefulness. Methods The 3D structure of Cav1.2 α1C subunit channel was obtained on basis of previous work (Saponara S. et al, 2015). The structure of flavons were downloaded from Pubchem(Kim S. et al, 2015). Docking simulation was carried out through Autodock/Vina v.1.1.2 (O.Trott et al, 2010). PDBePISAwas used in order to evaluate buried surface area values (B.S.A). Protein-ligand interactions were obtained using protein–ligand interaction profiler (P.L.I.P)(Salentin S. et al, 2015). Pymol was used as molecular graphics system (The PyMOL Molecular Graphics System, Version 1.8 Schrödinger, LLC.). Results and discussion I­­­­­n vitro analysis on rat Cav1.2 L-type channel of 20 flavonoids have shown stimulatory and inhibitory activities (Saponara S. et al, 2015).The 11 inhibitors and 8 stimulators derivatives are positioned in their corresponding binding-sites with peculiar sensing-residues interactions (shown in figure 1). Analyzing the network of interactions among the two classes of flavonoids we have observed hydrogen bonds, hydrophobic interactions and π–π stacking bonds characterizing their activities that could differently promote pore open/closed conformation and decreasing voltage-sensitive calcium channel activity (Tikhonov D. et al, 2009). Furthermore, on the basis of the selectivity filters model, we have evaluated B.S.A residues values present in the­­­ binding-sites, we have observed that B.S.A of some residues dramatically decrease, showing that these residues play a key role in the pore stabilization. The different mechanism of action of these molecules can be attributed to their chemical-physical proprieties as steric hindrance and different positions of hydroxyl groups.

scholarly journals Cdk5/p35 Regulates Neurotransmitter Release through Phosphorylation and Downregulation of P/Q-Type Voltage-Dependent Calcium Channel Activity

2002 ◽  
Vol 22 (7) ◽  
pp. 2590-2597 ◽  
Author(s):  
Kazuhito Tomizawa ◽  
Jun Ohta ◽  
Masayuki Matsushita ◽  
Akiyoshi Moriwaki ◽  
Sheng-Tian Li ◽  
...  
Keyword(s):  
Calcium Channel ◽  
Neurotransmitter Release ◽  
Channel Activity ◽  
Voltage Dependent Calcium Channel ◽  
Voltage Dependent

scholarly journals Identification of “on-off residues” in rat Cav1.2 α1C subunit channel using in silico analysis and docking simulation

2016 ◽  
Author(s):  
Alfonso Trezza ◽  
Andrea Bernini ◽  
Ottavia Spiga
Keyword(s):  
Calcium Channel ◽  
Mechanism Of Action ◽  
Binding Sites ◽  
Docking Simulation ◽  
Cardiac Contraction ◽  
Hydroxyl Groups ◽  
Channel Activity ◽  
Molecular Graphics ◽  
Ligand Interaction ◽  
Voltage Dependent

Introduction Voltage-dependent calcium channels (VSCC) is involved in important biological function as calcium ion transmembrane transport and cardiac contraction. VSCC is a multi-pass membrane protein, made up from α-1, α-2, β and δ subunits. α-1 subunit regulates the entry of ion calcium. Voltage-dependent L-type calcium channel subunit alpha-1C (Cav1.2 α1C subunit channel) is an isoform of VSCC, and is characterized from an high-voltage activation. Previous study have shown that class of molecules as benzothiazepines (Tikhonov D. et al, 2008), are able to block the alpha-1C subunit. Recent works have demonstrated that molecules belonged at the flavonoid class are able to inhibit or to raise channel activity (Saponara S. et al, 2011). In this work, we reported the sensing- residues that could play a key role in Cav1.2 α1C activity. Furthermore, we proposed a potential mechanism of action inside Cav1.2 α1C binding-site with differences between inhibitors and stimulants. Our work has clarifiedas the ligands operate on Cav1.2 α1C, this information could be useful in order to improve their usefulness. Methods The 3D structure of Cav1.2 α1C subunit channel was obtained on basis of previous work (Saponara S. et al, 2015). The structure of flavons were downloaded from Pubchem(Kim S. et al, 2015). Docking simulation was carried out through Autodock/Vina v.1.1.2 (O.Trott et al, 2010). PDBePISAwas used in order to evaluate buried surface area values (B.S.A). Protein-ligand interactions were obtained using protein–ligand interaction profiler (P.L.I.P)(Salentin S. et al, 2015). Pymol was used as molecular graphics system (The PyMOL Molecular Graphics System, Version 1.8 Schrödinger, LLC.). Results and discussion I­­­­­n vitro analysis on rat Cav1.2 L-type channel of 20 flavonoids have shown stimulatory and inhibitory activities (Saponara S. et al, 2015).The 11 inhibitors and 8 stimulators derivatives are positioned in their corresponding binding-sites with peculiar sensing-residues interactions (shown in figure 1). Analyzing the network of interactions among the two classes of flavonoids we have observed hydrogen bonds, hydrophobic interactions and π–π stacking bonds characterizing their activities that could differently promote pore open/closed conformation and decreasing voltage-sensitive calcium channel activity (Tikhonov D. et al, 2009). Furthermore, on the basis of the selectivity filters model, we have evaluated B.S.A residues values present in the­­­ binding-sites, we have observed that B.S.A of some residues dramatically decrease, showing that these residues play a key role in the pore stabilization. The different mechanism of action of these molecules can be attributed to their chemical-physical proprieties as steric hindrance and different positions of hydroxyl groups.

Scanning Mutagenesis Reveals a Role for Serine 189 of the Heterotrimeric G-Protein Beta 1 Subunit in the Inhibition of N-Type Calcium Channels

2006 ◽  
Vol 96 (1) ◽  
pp. 465-470 ◽  
Author(s):  
H. William Tedford ◽  
Alexandra E. Kisilevsky ◽  
Jean B. Peloquin ◽  
Gerald W. Zamponi
Keyword(s):  
Calcium Channel ◽  
G Protein ◽  
Neurotransmitter Release ◽  
Direct Contact ◽  
Channel Activity ◽  
Heterotrimeric G Protein ◽  
Channel Modulation ◽  
Opioid Drugs ◽  
Voltage Dependent ◽  
Dependent Inhibition

Direct interactions between the presynaptic N-type calcium channel and the β subunit of the heterotrimeric G-protein complex cause voltage-dependent inhibition of N-type channel activity, crucially influencing neurotransmitter release and contributing to analgesia caused by opioid drugs. Previous work using chimeras of the G-protein β subtypes Gβ1 and Gβ5 identified two 20–amino acid stretches of structurally contiguous residues on the Gβ1 subunit as critical for inhibition of the N-type channel. To identify key modulation determinants within these two structural regions, we performed scanning mutagenesis in which individual residues of the Gβ1 subunit were replaced by corresponding Gβ5 residues. Our results show that Gβ1 residue Ser189 is critical for N-type calcium channel modulation, whereas none of the other Gβ1 mutations caused statistically significant effects on the ability of Gβ1 to inhibit N-type channels. Structural modeling shows residue 189 is surface exposed, consistent with the idea that it may form a direct contact with the N-type calcium channel α1 subunit during binding interactions.

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