Receptors & Channels 

About: Receptors & Channels is an academic journal. The journal publishes majorly in the area(s): Receptor & G protein-coupled receptor. It has an ISSN identifier of 1060-6823. Over the lifetime, 321 publications have been published receiving 12093 citations.

Effects of external cations and mutations in the pore region on C-type inactivation of Shaker potassium channels.

Abstract: After removal of N-type inactivation in Shaker K channels another inactivation process remains (C-type inactivation) The C-type inactivation time course is reversibly slowed when external [K+] increases The effect of K+ is mimicked by Rb+ and, with less potency, by the less permeant ions Na+, Cs+, and NH4+ These results, which can be explained by the foot-in-the-door model of gating, could reflect the variable interaction of cations with amino acids in the ion-conducting pore Mutations at position 449 (near the outer mouth of the pore) produce drastic changes in C-type inactivation kinetics and in its interaction with monovalent cations Replacement of threonine in the wild-type by glutamic acid or lysine leads to a hundred-fold acceleration of inactivation (time constant approximately 25 ms) In contrast, placing valine at this position results in channels that do not inactivate in 45 s Moreover, high K+, besides slowing down the inactivation kinetics, produces an increase in current amplitude despite a concomitant decrease in K+ driving force This second effect, which is larger in mutants with faster inactivation kinetics, is caused by an increase in the number of channels that open on depolarization Thus, C-type inactivation is a process influenced by the ionic composition of the external milieu which strongly depends on the amino acid at position 449 in the pore region These findings may help to explain the variability in inactivation kinetics observed in the various types of K channels

Gcrdb: a g-protein-coupled receptor database

Abstract: G-protein-coupled receptors (GCRs) are a very large protein family and are critical components in many different autocrine, paracrine and endocrine signaling systems in animals. Current estimates are that humans have several thousand GCRs encoded by only slightly fewer genes. I have developed GCRDb, a database of sequences and other data relevant to the study of the biology of the receptors. The database implementation, data collection, and query system are described. An integral component of the design of GCRDb is the classification of GCRs in families. The current composition of GCRDb is presented in a table showing the number of entries in each family and group as derived from accepted mutation parsimony analyses.

Widespread expression of inositol 1,4,5-trisphosphate receptor type 1 gene (Insp3r1) in the mouse central nervous system.

Abstract: The expression of inositol 1,4,5-trisphosphate receptor type 1 (InsP3R1) in the mouse central nervous system (CNS) was studied by in situ hybridization. The receptor mRNAs were widely localized throughout the CNS, predominantly in the olfactory tubercle, cerebral cortex, CA1 pyramidal cell layer of the hippocampus, caudate putamen, and cerebellar Purkinje cells, where phosphoinositide turnover is known to be stimulated by various neurotransmitter receptors. In the most abundantly expressing Purkinje cells, InsP3R1 mRNA appeared to be translocated to the distal dendrites, since a strong hybridization density was observed in the molecular layer of the cerebellum. InsP3R protein is known to form tetrameric receptor-channel complex. Our preliminary hybridization data using probes for three distinct InsP3R subtypes showed preferential expression of InsP3R1 in many parts of the CNS. The expression of other receptor subtypes (InsP3R2 and InsP3R3) is less efficient, suggesting that a homotetramer formed of InsP3R1 subtype may play a central part in InsP3/Ca2+ signalling in the neuronal function, whereas a homotetramer of other subtypes and a possible heterotetramer among subtypes may be involved in differential InsP3/Ca2+ signalling. The chromosomal localization of the gene coding for InsP3R1 was confirmed on chromosome 6 but was found to be genetically independent of the Lurcher (Lc) mutation.

Characterization of and modulation by a beta-subunit of a human maxi KCa channel cloned from myometrium.

Abstract: cDNAs encoding functional maxi KCa channel alpha-subunits (hslo) were cloned from human myometrium. Northern blot analysis revealed a high abundance of mRNA in human uterine smooth muscle. Calcium- and voltage-activated K+ currents were recorded from Xenopus laevis oocytes injected with hslo cRNA and compared with currents after reconstitution of oocyte membranes expressing cloned maxi KCa channels. The expressed channels displayed characteristics of native maxi KCa channels, including large conductance (280 pS in symmetrical 110 mM K+), calcium sensitivity, kinetics and pharmacology. Currents were activated by niflumic acid; blocked by tetraethylammonium, charybdotoxin and iberiotoxin; and were insensitive to lemakalim, pinacidil, apamin and 4-aminopyridine. Coexpression with the beta-subunit, cloned from bovine trachea smooth muscle, dramatically increased the apparent calcium sensitivity as evident from a leftward shift of the voltage-activation curves. Half maximal activation (V1/2), measured in 10 microM Ca2+, was 12 +/- 18 mV (+/- SD, n = 62) for the alpha-subunit alone and -87 +/- 10 mV (+/- SD, n = 39) in presence of the beta-subunit.

VPAC Receptors for VIP and PACAP

Abstract: VIP and PACAP are two prominent neuropeptides that share two common G protein-coupled receptors, VPAC1 and VPAC2, while PACAP has an additional specific receptor, PAC1. This article reviews the present knowledge regarding various aspects of VPAC receptors including: 1) receptor specificity toward natural VIP-related peptides and pharmacology of synthetic agonists or antagonists; 2) genomic organization and chromosomal localization; 3) signaling and established or putative interactions with G proteins or accessory proteins such as RAMPs or PDZ-containing proteins; 4) molecular basis of ligand-receptor interaction as determined by site-directed mutagenesis, construction of receptor chimeras, and structural modeling; 5) constitutively active receptor mutants; 6) short-term (desensitization, internalization, phosphorylation) and long-term (transcription) regulations and transgenic models; 7) receptor polymorphisms.