Tags

Type your tag names separated by a space and hit enter

Electrostatics in the cytoplasmic pore produce intrinsic inward rectification in kir2.1 channels.
J Gen Physiol. 2005 Dec; 126(6):551-62.JG

Abstract

Inward rectifier K+ channels are important in regulating membrane excitability in many cell types. The physiological functions of these channels are related to their unique inward rectification, which has been attributed to voltage-dependent block. Here, we show that inward rectification can also be induced by neutral and positively charged residues at site 224 in the internal vestibule of tetrameric Kir2.1 channels. The order of extent of inward rectification is E224K mutant > E224G mutant > wild type in the absence of internal blockers. Mutating the glycines at the equivalent sites to lysines also rendered weak inward rectifier Kir1.1 channels more inwardly rectifying. Also, conjugating positively charged methanethiosulfonate to the cysteines at site 224 induced strong inward rectification, whereas negatively charged methanethiosulfonate alleviated inward rectification in the E224C mutant. These results suggest that charges at site 224 may control inward rectification in the Kir2.1 channel. In a D172N mutant, spermine interacting with E224 and E299 induced channel inhibition during depolarization but did not occlude the pore, further suggesting that a mechanism other than channel block is involved in the inward rectification of the Kir2.1 channel. In this and our previous studies we showed that the M2 bundle crossing and selectivity filter were not involved in the inward rectification induced by spermine interacting with E224 and E299. We propose that neutral and positively charged residues at site 224 increase a local energy barrier, which reduces K+ efflux more than K+ influx, thereby producing inward rectification.

Authors+Show Affiliations

Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16316974

Citation

Yeh, Shih-Hao, et al. "Electrostatics in the Cytoplasmic Pore Produce Intrinsic Inward Rectification in Kir2.1 Channels." The Journal of General Physiology, vol. 126, no. 6, 2005, pp. 551-62.
Yeh SH, Chang HK, Shieh RC. Electrostatics in the cytoplasmic pore produce intrinsic inward rectification in kir2.1 channels. J Gen Physiol. 2005;126(6):551-62.
Yeh, S. H., Chang, H. K., & Shieh, R. C. (2005). Electrostatics in the cytoplasmic pore produce intrinsic inward rectification in kir2.1 channels. The Journal of General Physiology, 126(6), 551-62.
Yeh SH, Chang HK, Shieh RC. Electrostatics in the Cytoplasmic Pore Produce Intrinsic Inward Rectification in Kir2.1 Channels. J Gen Physiol. 2005;126(6):551-62. PubMed PMID: 16316974.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Electrostatics in the cytoplasmic pore produce intrinsic inward rectification in kir2.1 channels. AU - Yeh,Shih-Hao, AU - Chang,Hsueh-Kai, AU - Shieh,Ru-Chi, PY - 2005/12/1/pubmed PY - 2006/3/24/medline PY - 2005/12/1/entrez SP - 551 EP - 62 JF - The Journal of general physiology JO - J Gen Physiol VL - 126 IS - 6 N2 - Inward rectifier K+ channels are important in regulating membrane excitability in many cell types. The physiological functions of these channels are related to their unique inward rectification, which has been attributed to voltage-dependent block. Here, we show that inward rectification can also be induced by neutral and positively charged residues at site 224 in the internal vestibule of tetrameric Kir2.1 channels. The order of extent of inward rectification is E224K mutant > E224G mutant > wild type in the absence of internal blockers. Mutating the glycines at the equivalent sites to lysines also rendered weak inward rectifier Kir1.1 channels more inwardly rectifying. Also, conjugating positively charged methanethiosulfonate to the cysteines at site 224 induced strong inward rectification, whereas negatively charged methanethiosulfonate alleviated inward rectification in the E224C mutant. These results suggest that charges at site 224 may control inward rectification in the Kir2.1 channel. In a D172N mutant, spermine interacting with E224 and E299 induced channel inhibition during depolarization but did not occlude the pore, further suggesting that a mechanism other than channel block is involved in the inward rectification of the Kir2.1 channel. In this and our previous studies we showed that the M2 bundle crossing and selectivity filter were not involved in the inward rectification induced by spermine interacting with E224 and E299. We propose that neutral and positively charged residues at site 224 increase a local energy barrier, which reduces K+ efflux more than K+ influx, thereby producing inward rectification. SN - 0022-1295 UR - https://www.unboundmedicine.com/medline/citation/16316974/Electrostatics_in_the_cytoplasmic_pore_produce_intrinsic_inward_rectification_in_kir2_1_channels_ L2 - https://rupress.org/jgp/article-lookup/doi/10.1085/jgp.200509367 DB - PRIME DP - Unbound Medicine ER -