Biology subjects

Tateyama, M.

Publications and source records attributed to Tateyama, M..

3 recordsLinked to original sources

bioRxiv2023

Structural determinants of the direct inhibition of GIRK channels by Sigma-1 receptor antagonist

G-protein-gated inward rectifier K+ (GIRK) channels play critical roles in the regulation of the excitability of cardiomyocytes and neurons and include GIRK1, GIRK2, GIRK3 and GIRK4 subfamily members. BD1047 dihydrobromide (BD1047) is one of the representative antagonists of multi-functional Sigma-1 receptor (S1R). In the analysis of the effect of BD1047 on the inhibition of Gi-coupled receptors by S1R using GIRK channel as an effector, we observed that BD1047 directly inhibits GIRK current even in the absence of S1R. Thus, we aimed to clarify the effect of BD1047 on GIRK channels and its structural determinants. By electrophysiological recordings in Xenopus oocytes, we observed that BD1047 directly inhibited the current of GIRK channels, producing a much stronger inhibition of GIRK4 channels compared to GIRK2. It also inhibited the ACh-induced native GIRK current in isolated rat atrial myocytes. Chimeric and mutagenesis studies of GIRK2 and GIRK4 combining with molecular docking analysis, demonstrate the importance of the Leu77 on the proximal N-terminal cytoplasmic region of GIRK4 for the inhibition by BD1047. The activator of GIRK channel, ivermectin, competed with BD1047 at Leu77 on GIRK4. This study provides us with a novel inhibitor of GIRK channels and information for developing pharmacological treatments for GIRK4 associated diseases. Key pointsO_LISigma-1 receptor antagonist, BD1047, directly inhibits the current of GIRK channels. It strongly inhibits GIRK4 channels but only weakly inhibits GIRK2. C_LIO_LIBD1047 inhibits the ACh-induced GIRK current in isolated rat atrial myocyte. C_LIO_LILeu77 on the proximal N-terminal of GIRK4 is essential for the inhibition by BD1047. C_LIO_LIBinding of BD1047 adjacent to Leu77, but not to Leu77Ile, was confirmed by molecular docking analysis. C_LIO_LIThe activator of GIRK channel, ivermectin, competes with BD1047 at Leu77 on GIRK4. C_LI

biophysics↗

bioRxiv2019

A native prokaryotic voltage-dependent calcium channel with a novel selectivity filter sequence

Voltage-dependent Ca2+ channels (Cavs) are indispensable for coupling action potentials with Ca2+ signaling in living organisms. The structure of Cavs is similar to that of voltage-dependent Na+ channels (Navs). It is known that prokaryotic Navs can obtain Ca2+ selectivity by negative charge mutations of the selectivity filter, but native prokaryotic Cavs had not yet been identified.\n\nHere, we report the first identification of a native prokaryotic Cav, CavMr, and its relative, NavPp. Although CavMr contains a smaller number of negatively charged residues in the selectivity filter than artificial prokaryotic Cavs, CavMr exhibits high Ca2+ selectivity. In contrast, NavPp, which has similar filter sequence to artificial Cavs, mainly allows Na+ to permeate. Interestingly, a NavPp mutant whose selectivity filter was replaced with that of CavMr exhibits high Ca2+ selectivity. Mutational analyses revealed that the glycine residue of the CavMr selectivity filter is a determinant for Ca2+ selectivity. This glycine residue is well conserved among subdomains I and III of eukaryotic Cavs.\n\nThese findings provide new insight into the Ca2+ selectivity mechanism conserved from prokaryotes to eukaryotes.

biophysics↗

bioRxiv2018

SLO potassium channels antagonize premature decision making in C. elegans

SummaryAnimals have to modify their behavior at the right timing to respond to changes in environments. Yet, the molecular and neural mechanisms regulating the timing of behavioral transition remain largely unknown. Performing forward genetics on a plasticity of thermotaxis behavior in C. elegans, we demonstrated that SLO potassium channels together with a cyclic nucleotide-gated channel CNG-3 determine the timing of the transition of temperature preference after shift of cultivation temperature. We further revealed that SLO and CNG-3 channels regulate the alteration in responsiveness of thermosensory neurons. Our results suggest that the regulation of sensory adaptation is a major determinant of the latency for animals to make decisions in changing behavior.\n\nHighlightsO_LISlo-1 and SLO-2 K+ channels decelerated transition of temperature preference in thermotaxis behavior after upshift of cultivation temperature\nC_LIO_LISLO K+ channels slowed down the adaptation of AFD thermosensory neuron to new cultivation temperature\nC_LIO_LIA cyclic nucleotide-gated channel CNG-3 functioned together with SLO-2\nC_LIO_LIThermotaxis serves as could be a model system for early onset epilepsies\nC_LI

neuroscience↗