Posts Tagged: calcium channels

Calcium Signaling and Cardiac Arrhythmias

Calcium Signaling and Cardiac Arrhythmias

Andrew P. Landstrom, Dobromir Dobrev, Xander H.T. Wehrens

Ryanodine receptor type-2 (RyR2) macromolecular complex. Cartoon representing RyR2 pore-forming subunits with accessory proteins that bind to and/or modulate channel function. CaM indicates calmodulin; CaMKII, Ca2+/calmodulin-dependent protein kinase II; CASQ2, calsequestrin-2; FKBP12.6, FK506-binding protein-12.6; JCTN, junctin; JPH2, juncophilin-2; PKA, protein kinase A; PM, plasma membrane; PP, protein phosphatase; SR, sarcoplasmic reticulum; TECRL, trans-2,3-enoyl-CoA reductase-like protein; and TRDN; triadin. [Powerpoint File]

Calcium Signaling and Cardiac Arrhythmias

Calcium Signaling and Cardiac Arrhythmias

Andrew P. Landstrom, Dobromir Dobrev, Xander H.T. Wehrens

Role of calcium-handling in excitation–contraction (EC) coupling. A, Schematic overview of key Ca2+-handling proteins involved in EC coupling. B, Schematic diagram of Ca2+ release unit and major components of the JMC (junctional membrane complex). The transverse tubule (TT) and sarcoplasmic reticulum (SR) membranes approximate to form the dyad. BIN1 indicates bridging integrator 1; Cav1.2, L-type Ca2+ channel; CAV3, caveolin-3; JPH2, juncophilin-2; NCX1, Na+/Ca2+ exchanger type-1; PM, plasma membrane; PMCA, plasmalemmal Ca2+-ATPase; RyR2, ryanodine receptor type-2; and SERCA2a, sarco/endoplasmic reticulum ATPase type-2a.* [Powerpoint File]

Regulation of Cardiac L-Type Ca2+ Channel CaV1.2 Via the β-Adrenergic-cAMP-Protein Kinase A Pathway: Old Dogmas, Advances, and New Uncertainties

Regulation of Cardiac L-Type Ca2+ Channel CaV1.2 Via the β-Adrenergic-cAMP-Protein Kinase A Pathway: Old Dogmas, Advances, and New Uncertainties

Sharon Weiss, Shimrit Oz, Adva Benmocha, Nathan Dascal

Topology, subunits, and important sites of the L-type Ca2+ channel (CaV1.2): α1C, the main pore-forming subunit, and auxiliary subunits β2 and α2/δ. α1C is a target for protein kinase A (PKA) phosphorylation on residues along its C terminus (CT): Ser1700, Thr1704, Ser1928. Cardiac α1C undergoes post-translational proteolytic cleavage at a.a. 1800. A kinase anchoring proteins (AKAPs), which may also play a role in the adrenergic modulation of the channel, bind to the distal part of the CT. Also indicated are the calmodulin-binding pre-IQ and IQ domains,124 and several other amino acid residues which are mentioned in the text. All numbering is according to the rabbit α1C, the first cDNA of an α1C cloned69 (GenBank accession number X15539). In the names of protein domains (EF hand and IQ domain), capital letters refer to amino acids glutamate (E), phenylalanine (F), isoleucine (I) and glutamine (Q). AID indicates α1 interaction domain. [Powerpoint File]

Regulation of Cardiac L-Type Ca2+ Channel CaV1.2 Via the β-Adrenergic-cAMP-Protein Kinase A Pathway: Old Dogmas, Advances, and New Uncertainties

Regulation of Cardiac L-Type Ca2+ Channel CaV1.2 Via the β-Adrenergic-cAMP-Protein Kinase A Pathway: Old Dogmas, Advances, and New Uncertainties

Sharon Weiss, Shimrit Oz, Adva Benmocha, Nathan Dascal

A schematic drawing of the β-adrenergic receptors (β-AR) signaling cascade. Agonist binding to β-AR activates Gαs followed by adenylyl cyclase (AC). cAMP levels rise and protein kinase A (PKA) is activated. The main target of PKA in this modulation is CaV1.2, which is located in the plasma membrane and along the T-tubules. AKAP indicates A kinase anchoring protein; CT, C terminus; NT, N terminus; and RyR, ryanodine receptor. [Powerpoint File]