Anion conductance selectivity mechanism of the CFTR chloride channel

Biochimica Et Biophysica Acta
P Linsdell

Abstract

All ion channels are able to discriminate between substrate ions to some extent, a process that involves specific interactions between permeant anions and the so-called selectivity filter within the channel pore. In the cystic fibrosis transmembrane conductance regulator (CFTR) anion-selective channel, both anion relative permeability and anion relative conductance are dependent on anion free energy of hydration--anions that are relatively easily dehydrated tend to show both high permeability and low conductance. In the present work, patch clamp recording was used to investigate the relative conductance of different anions in CFTR, and the effect of mutations within the channel pore. In constitutively-active E1371Q-CFTR channels, the anion conductance sequence was Cl(-) > NO3(-) > Br(-) > formate > SCN(-) > I(-). A mutation that disrupts anion binding in the inner vestibule of the pore (K95Q) disrupted anion conductance selectivity, such that anions with different permeabilities showed almost indistinguishable conductances. Conversely, a mutation at the putative narrowest pore region that is known to disrupt anion permeability selectivity (F337A) had minimal effects on anion relative conductance. Ion competition experiments con...Continue Reading

References

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Citations

Oct 9, 2016·Cellular and Molecular Life Sciences : CMLS·Isabelle CallebautJean-Paul Mornon
Oct 5, 2016·Cellular and Molecular Life Sciences : CMLS·Paul Linsdell
Dec 6, 2018·Physiological Reviews·László CsanádyDavid C Gadsby
Feb 14, 2019·Cellular and Molecular Life Sciences : CMLS·Alexander NegodaPaul Linsdell
May 23, 2020·Scientific Reports·Michele FioreOscar Moran
Mar 28, 2018·The Journal of General Physiology·Tzyh-Chang HwangSamantha Destefano
Apr 6, 2017·Journal of Experimental Botany·Stefanie WegeSam W Henderson
Feb 14, 2018·Endocrine-related Cancer·Antonio De la Vieja, Pilar Santisteban
May 26, 2021·Cell Biochemistry and Biophysics·Paul Linsdell

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