Abstract

This proposal investigates the molecular mechanisms of K selectivity and inward rectification in IRK channels expressed in Xenopus oocytes. In particular, the investigator will investigate the selectivity of the K binding site using selective IRK channel mutants, and rectification that results from intracellular blocking ions. The ROMK1 and IRK1 channels are appropriate channels on which to carry out these investigations. The mutant channels that conduct fall into two categories: those that have ion selectivity like WT channel and those that are nonselective. The proposal investigates the mechanisms rectification and the interactions of specific polyamines with rectifying channels.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM055560-05
Application #
6386665
Study Section
Physiology Study Section (PHY)
Program Officer
Shapiro, Bert I
Project Start
1997-05-01
Project End
2002-04-30
Budget Start
2001-05-01
Budget End
2002-04-30
Support Year
5
Fiscal Year
2001
Total Cost
$236,642
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Physiology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Pau, Victor; Zhou, Yufeng; Ramu, Yajamana et al. (2017) Crystal structure of an inactivated mutant mammalian voltage-gated K+ channel. Nat Struct Mol Biol 24:857-865
Combs, David J; Lu, Zhe (2015) Sphingomyelinase D inhibits store-operated Ca2+ entry in T lymphocytes by suppressing ORAI current. J Gen Physiol 146:161-72
Ramu, Yajamana; Xu, Yanping; Shin, Hyeon-Gyu et al. (2014) Counteracting suppression of CFTR and voltage-gated K+ channels by a bacterial pathogenic factor with the natural product tannic acid. Elife 3:e03683
Xu, Yanping; Ramu, Yajamana; Shin, Hyeon-Gyu et al. (2013) Energetic role of the paddle motif in voltage gating of Shaker K(+) channels. Nat Struct Mol Biol 20:574-81
Combs, David J; Shin, Hyeon-Gyu; Xu, Yanping et al. (2013) Tuning voltage-gated channel activity and cellular excitability with a sphingomyelinase. J Gen Physiol 142:367-80
Xu, Yanping; Ramu, Yajamana; Lu, Zhe (2010) A shaker K+ channel with a miniature engineered voltage sensor. Cell 142:580-9
Xu, Yanping; Shin, Hyeon-Gyu; Szép, Szilvia et al. (2009) Physical determinants of strong voltage sensitivity of K(+) channel block. Nat Struct Mol Biol 16:1252-8