Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Genes related to trp (transient receptor potential) are proposed to encode store-operated channels. We examined the ionic permeation of recombinant channels formed by stable and transient expression of the TRP homologue bCCE1 in Chinese hamster ovary (CHO) cells (CHO(CCE1)) and rat basophilic leukaemia (RBL) cells, respectively. 2. Store-operated currents were activated in CHO(CCE1) cells by internal dialysis of IP3 under strong buffering of intracellular Ca2+. The action of IP3 was mimicked by thapsigargin but not by IP4. 3. With extracellular Ca2+, Na+ and Mg2+, the store-operated currents of CHO(CCE1) rectified inwardly in the presence of internal Cs+. Outward currents were not detected below +80 mV. Identical currents were recorded with external Ba2+ and also with no external Na+ and Mg2+. In the absence of external Mg2+, the inward currents showed an anomalous mole fraction behaviour between Ca2+ and Na+. Half-maximal inhibition of Na+ currents was observed with approximately 100 nM and full block with 2-5 microM external Ca2+. 4. In the parental CHO(-) cells, IP3 dialysis evoked inward currents that also displayed anomalous mole fraction behaviour between Ca2+ and Na+. However, half-maximal block of Na+ currents required 5 times higher Ca2+ concentrations in CHO(-) cells. Additionally, the density of Ca2+ and Na+ currents at -80 mV was 5 and 2 times larger in CHO(CCE1) cells, respectively. 5. In RBL cells, dialysis of IP3 evoked store-operated currents that showed 1.4-fold larger densities at -80 mV in cells expressing bCCE1. 6. The enhanced density of store-operated currents in CHO(CCE1) cells and in bCCE1-transfected RBL cells probably reflects the phenotype of CCE1. These results suggest a highly selective permeation of Ca2+ through recombinant channels formed by CCE1 either alone or in combination with endogenous channel proteins.
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PMID:Phenotype of a recombinant store-operated channel: highly selective permeation of Ca2+. 1042 2

Polycystin-2 (PC2, TRPP2) is a TRP-type, non-selective cation channel whose dysfunction is implicated in changes in primary cilium structure and genesis of autosomal dominant polycystic kidney disease (ADPKD). Lithium (Li(+)) is a potent pharmaceutical agent whose effect on cell function is largely unknown. In this work, we explored the effect of Li(+) on PC2 channel function. In vitro translated PC2 was studied in a lipid bilayer reconstitution system exposed to different chemical conditions such as Li(+) or K(+) chemical gradients and different symmetrical concentrations of either cation. Li(+) inhibited PC2 function only from the external side, by decreasing the single-channel conductance and modifying the reversal potential consistent with both permeability to and blockage of the channel. When a chemical gradient was imposed, the PC2 single-channel conductance was 144 pS and 107 pS for either K(+) or Li(+), respectively. Data were analysed in terms of the Goldman-Hodgkin-Katz approximation and energy models based on absolute rate theory to understand the mechanism(s) of Li(+) transport and blockage of PC2. The 2S3B model better explained the findings, including saturation, anomalous mole fraction, non-linearity of the current-voltage curves under bi-ionic conditions and concentration dependence of permeability ratios. The data indicate that Li(+) modifies PC2 channel function, whose effect unmasks a high-affinity binding site for this ion, and an intrinsic asymmetry in the pore structure of the channel. The findings provide insights into possible mechanism(s) of Li(+) regulation of ciliary length and dysfunction mediated by this cation.
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PMID:Effect of lithium on the electrical properties of polycystin-2 (TRPP2). 2167 23

Transient receptor potential melastatin 8 (TRPM8) is a cold-sensitive ion channel with diverse physiological roles. TRPM8 activity is modulated by many mechanisms, including an interaction with the small membrane protein phosphoinositide-interacting regulator of TRP (PIRT). Here, using comparative electrophysiology experiments, we identified species-dependent differences between the human and mouse TRPM8-PIRT complexes. We found that human PIRT attenuated human TPRM8 conductance, unlike mouse PIRT, which enhanced mouse TRPM8 conductance. Quantitative Western blot analysis demonstrates that this effect does not arise from decreased trafficking of TRPM8 to the plasma membrane. Chimeric human/mouse TRPM8 channels were generated to probe the molecular basis of the PIRT modulation, and the effect was recapitulated in a pore domain chimera, demonstrating the importance of this region for PIRT-mediated regulation of TRPM8. Moreover, recombinantly expressed and purified human TRPM8 S1-S4 domain (comprising transmembrane helices S1-S4, also known as the sensing domain, ligand-sensing domain, or voltage sensing-like domain) and full-length human PIRT were used to investigate binding between the proteins. NMR experiments, supported by a pulldown assay, indicated that PIRT binds directly and specifically to the TRPM8 S1-S4 domain. Binding became saturated as the S1-S4:PIRT mole ratio approached 1. Our results have uncovered species-specific TRPM8 modulation by PIRT. They provide evidence for a direct interaction between PIRT and the TRPM8 S1-S4 domain with a 1:1 binding stoichiometry, suggesting that a functional tetrameric TRPM8 channel has four PIRT-binding sites.
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PMID:Phosphoinositide-interacting regulator of TRP (PIRT) has opposing effects on human and mouse TRPM8 ion channels. 2972 21