Yoshihiro Kubo

Bio: Yoshihiro Kubo is an academic researcher from National Institutes of Natural Sciences, Japan. The author has contributed to research in topics: Gating & Voltage clamp. The author has an hindex of 38, co-authored 131 publications receiving 6175 citations. Previous affiliations of Yoshihiro Kubo include Graduate University for Advanced Studies & University of Tokyo.

Primary structure and functional expression of a mouse inward rectifier potassium channel

Abstract: A complementary DNA encoding an inward rectifier K+ channel (IRK1) was isolated from a mouse macrophage cell line by expression cloning. This channel conducts inward K+ current below the K+ equilibrium potential but passes little outward K+ current. The IRK1 channel contains only two putative transmembrane segments per subunit and corresponds to the inner core structure of voltage-gated K+ channels. The IRK1 channel and an ATP-regulated K+ channel show extensive sequence similarity and constitute a new superfamily.

Primary structure and functional expression of a rat G-protein-coupled muscarinic potassium channel

Abstract: Parasympathetic nerve stimulation causes slowing of the heart rate by activation of muscarinic receptors and the subsequent opening of muscarinic K+ channels in the sinoatrial node and atrium. This inwardly rectifying K+ channel is coupled directly with G protein. Based on sequence homology with cloned inwardly rectifying K+ channels, ROMK1 (ref. 11) and IRK1 (ref. 12), we have isolated a complementary DNA for a G-protein-coupled inwardly rectifying K+ channel (GIRK1) from rat heart. The GIRK1 channel probably corresponds to the muscarinic K+ channel because (1) its functional properties resemble those of the atrial muscarinic K+ channel and (2) its messenger RNA is much more abundant in the atrium than in the ventricle. In addition, GIRK1 mRNA is expressed not only in the heart but also in the brain.

A mammalian neural tissue opsin (Opsin 5) is a deep brain photoreceptor in birds

Abstract: It has been known for many decades that nonmammalian vertebrates detect light by deep brain photoreceptors that lie outside the retina and pineal organ to regulate seasonal cycle of reproduction. However, the identity of these photoreceptors has so far remained unclear. Here we report that Opsin 5 is a deep brain photoreceptive molecule in the quail brain. Expression analysis of members of the opsin superfamily identified as Opsin 5 (OPN5; also known as Gpr136, Neuropsin, PGR12, and TMEM13) mRNA in the paraventricular organ (PVO), an area long believed to be capable of phototransduction. Immunohistochemistry identified Opsin 5 in neurons that contact the cerebrospinal fluid in the PVO, as well as fibers extending to the external zone of the median eminence adjacent to the pars tuberalis of the pituitary gland, which translates photoperiodic information into neuroendocrine responses. Heterologous expression of Opsin 5 in Xenopus oocytes resulted in light-dependent activation of membrane currents, the action spectrum of which showed peak sensitivity (λmax) at ∼420 nm. We also found that short-wavelength light, i.e., between UV-B and blue light, induced photoperiodic responses in eye-patched, pinealectomized quail. Thus, Opsin 5 appears to be one of the deep brain photoreceptive molecules that regulates seasonal reproduction in birds.

International Union of Pharmacology. LIV. Nomenclature and Molecular Relationships of Inwardly Rectifying Potassium Channels

Abstract: Since the initial cDNA cloning of the first inward rectifiers Kir11 (ROMK1) and Kir21 (IRK1) in 1993, a succession of new members of this family have been identified, including the G protein-coupled Kir3 and the ATP-sensitive Kir6 These channels play an important physiological role in the

Structural Basis for a Ca2+-Sensing Function of the Metabotropic Glutamate Receptors

Abstract: The metabotropic glutamate receptors (mGluRs) are widely distributed in the brain and play important roles in synaptic plasticity. Here it is shown that some types of mGluRs are activated not only by glutamate but also by extracellular Ca2+ (Ca2+o). A single amino acid residue was found to determine the sensitivity of mGluRs to Ca2+o. One of the receptors, mGluR1alpha, but not its point mutant with reduced sensitivity to Ca2+o, caused morphological changes when transfected into mammalian cells. Thus, the sensing of Ca2+o by mGluRs may be important in cells under physiological condition.

Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans

Abstract: Experimental introduction of RNA into cells can be used in certain biological systems to interfere with the function of an endogenous gene Such effects have been proposed to result from a simple antisense mechanism that depends on hybridization between the injected RNA and endogenous messenger RNA transcripts RNA interference has been used in the nematode Caenorhabditis elegans to manipulate gene expression Here we investigate the requirements for structure and delivery of the interfering RNA To our surprise, we found that double-stranded RNA was substantially more effective at producing interference than was either strand individually After injection into adult animals, purified single strands had at most a modest effect, whereas double-stranded mixtures caused potent and specific interference The effects of this interference were evident in both the injected animals and their progeny Only a few molecules of injected double-stranded RNA were required per affected cell, arguing against stochiometric interference with endogenous mRNA and suggesting that there could be a catalytic or amplification component in the interference process

Ion Channels in Excitable Membranes

Abstract: Excitability. Excitability of cell membranes is crucial for signaling in many types of cell. Excitation in the physiological sense means that the cell membrane potential undergoes characteristic changes which, in most cases, go in the depolarizing direction. Single depolarization from the resting potential to potentials near 0 mV has generally been called an action potential. A schematic representation of a neuronal action potential is given in Fig. 12.1 A. The action potential is triggered when the membrane potential, which was at the resting level, depolarizes and reaches the threshold of excitation. This depolarization, which triggers the action potential, is generated by depolarizing synaptic currents, or depolarizing current coming from a membrane region that is already excited (propagation of an action potential), or by pacemaker currents mediated by pacemaker channels, or by current injected externally by an electrode. The duration of different types of action potential varies from seconds to less than 1 ms.

Flow-mediated endothelial mechanotransduction

Abstract: Mechanical forces associated with blood flow play important roles in the acute control of vascular tone, the regulation of arterial structure and remodeling, and the localization of atherosclerotic lesions. Major regulation of the blood vessel responses occurs by the action of hemodynamic shear stresses on the endothelium. The transmission of hemodynamic forces throughout the endothelium and the mechanotransduction mechanisms that lead to biophysical, biochemical, and gene regulatory responses of endothelial cells to hemodynamic shear stresses are reviewed.

Physiological roles and properties of potassium channels in arterial smooth muscle

Abstract: This review examines the properties and roles of the four types of K+ channels that have been identified in the cell membrane of arterial smooth muscle cells. 1) Voltage-dependent K+ (KV) channels increase their activity with membrane depolarization and are important regulators of smooth muscle membrane potential in response to depolarizing stimuli. 2) Ca(2+)-activated K+ (KCa) channels respond to changes in intracellular Ca2+ to regulate membrane potential and play an important role in the control of myogenic tone in small arteries. 3) Inward rectifier K+ (KIR) channels regulate membrane potential in smooth muscle cells from several types of resistance arteries and may be responsible for external K(+)-induced dilations. 4) ATP-sensitive K+ (KATP) channels respond to changes in cellular metabolism and are targets of a variety of vasodilating stimuli. The main conclusions of this review are: 1) regulation of arterial smooth muscle membrane potential through activation or inhibition of K+ channel activity provides an important mechanism to dilate or constrict arteries; 2) KV, KCa, KIR, and KATP channels serve unique functions in the regulation of arterial smooth muscle membrane potential; and 3) K+ channels integrate a variety of vasoactive signals to dilate or constrict arteries through regulation of the membrane potential in arterial smooth muscle.

Genetic organization and diversity of the hepatitis C virus.

Abstract: The nucleotide sequence of the RNA genome of the human hepatitis C virus (HCV) has been determined from overlapping cDNA clones. The sequence (9379 nucleotides) has a single large open reading frame that could encode a viral polyprotein precursor of 3011 amino acids. While there as little overall amino acid and nucleotide sequence homology with other viruses, the 5' HCV nucleotide sequence upstream of this large open reading frame has substantial similarity to the 5' termini of pestiviral genomes. The polyprotein also has significant sequence similarity to helicases encoded by animal pestiviruses, plant potyviruses, and human flaviviruses, and it contains sequence motifs widely conserved among viral replicases and trypsin-like proteases. A basic, presumed nucleocapsid domain is located at the N terminus upstream of a region containing numerous potential N-linked glycosylation sites. These HCV domains are located in the same relative position as observed in the pestiviruses and flaviviruses and the hydrophobic profiles of all three viral polyproteins are similar. These combined data indicate that HCV is an unusual virus that is most related to the pestiviruses. Significant genome diversity is apparent within the putative 5' structural gene region of different HCV isolates, suggesting the presence of closely related but distinct viral genotypes.