Voltage-dependent sodium channels from a variety of tissues are known to be phosphorylated by the cAMP-dependent protein kinase, protein kinase A. However, the functional significance of sodium channel phosphorylation is not clearly understood. Using whole-cell voltage-clamp techniques, we show that sodium currents (INas) in rabbit cardiac myocytes are enhanced by isoproterenol (ISO). This enha...

Negative regulation of the heartbeat rate involves the activation of an inwardly rectifying potassium current (I(KACh)) by G protein-coupled receptors such as the m2 muscarinic acetylcholine receptor. Recent studies have shown that this process involves the direct binding of G(betagamma) subunits to the NH(2)- and COOH-terminal cytoplasmic domains of the proteins termed GIRK1 and GIRK4 (Kir3.1 ...

Site-directed mutagenesis was used to mutate aCys418 and (3Cys447 in the M4 domain of Torpedo califomica acetylcholine receptor expressed in Xenopus laevis oocytes. The M4 region is a transmembrane domain thought to be located at the lipid-protein interface. By whole-cell voltage clamp analysis, mutation of both a subunits to aTrp418 increased maximal channel activity approximately threefold, i...

Detergent extracts of cell envelopes of the gliding bacterium Herpetosiphon aurantiacus formed channels in lipid bilayers. Fast protein liquid chromatography across a HiTrap-Q cation-exchange column demonstrated that a 45-kDa protein forms the channel. The observation of a channel-forming protein suggests that Herpetosiphon aurantiacus Hp a2 has a permeability barrier on its surface.

We have investigated the role of membrane proteins and lipids during early phases of the cotranslational insertion of secretory proteins into the translocation channel of the endoplasmic reticulum (ER) membrane. We demonstrate that all steps, including the one during which signal sequence recognition occurs, can be reproduced with purified translocation components in detergent solution, in the ...

Background—The sarcoplasmic reticulum (SR) Ca-release channel plays a key role in the excitation-contraction coupling of cardiac myocytes. Because respective alterations have been reported in human heart failure, we investigated isoform expression of the SR Ca-release channel in human hearts from patients with terminal heart failure (dilated cardiomyopathy [DCM], n58) and nonfailing organ donor...

Use of randomized peptide libraries to evolve molecules with new functions provides a means for developing novel regulators of protein activity. Despite the demonstrated power of such approaches for soluble targets, application of this strategy to membrane systems, such as ion channels, remains challenging. Here, we have combined libraries of a tethered protein scaffold with functional selectio...

BACKGROUND Sustained shortening of the atrial effective refractory period (AERP), probably due to reduction in the L-type calcium current, is a major factor in the initiation and maintenance of atrial fibrillation (AF). We investigated underlying molecular changes by studying the relation between gene expression of the L-type calcium channel and potassium channels and AERP in patients with AF. ...

Ion channel receptors are a vital component of nervous system signaling, allowing rapid and direct conversion of a chemical neurotransmitter message to an electrical current. In recent decades, it has become apparent that ionotropic receptors are regulated by protein-protein interactions with other ion channels, G-protein coupled receptors and intracellular proteins. These other proteins can al...

We present a method of constructing the volume meshes of the membrane-channel protein system for finite element simulation of ion channels. The membrane channel system consists of the solvent region and the membrane-protein region. Our method focuses on labeling the tetrahedra in the solvent and membrane-protein regions and collecting the interface triangles between different regions. It contai...