Ionic selectivity revisited: The role of kinetic and equilibrium processes in ion permeation through channels

Eisenman, George; Horn, Richard

doi:10.1007/bf01870364

Cited by 528 publications

(440 citation statements)

References 95 publications

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“…We examined the anion selectivity sequence of mBest3-induced current and found SCN Ϫ ϾI Ϫ ϾCl Ϫ , which follows the Eisenman "weak field strength" lyotrophic series (10). This permeability sequence is identical to that described for cardiac I ClCa and Cl Ϫ currents elicited by expression of mBest2 (34) and truncated mBest3 (33).…”

Section: Discussionmentioning

confidence: 61%

Expression, localization, and functional properties of Bestrophin 3 channel isolated from mouse heart

O'Driscoll¹,

Hatton²,

Burkin³

et al. 2008

American Journal of Physiology-Cell Physiology

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Bestrophins are a novel family of proteins that encode calcium-activated chloride channels. In this study we establish that Bestrophin transcripts are expressed in the mouse and human heart. Native mBest3 protein expression and localization in heart was demonstrated by using a specific polyclonal mBest3 antibody. Immunostaining of isolated cardiac myocytes indicates that mBest3 is present at the membrane. Using the patch-clamp technique, we characterized the biophysical and pharmacological properties of mBest3 cloned from heart. Whole cell chloride currents were evoked in both HEK293 and COS-7 cells expressing mBest3 by elevation of intracellular calcium. mBest3 currents displayed a KD for Ca 2ϩ of ϳ175 nM. The calcium-activated chloride current was found to be time and voltage independent and displayed slight outward rectification. The anion permeability sequence of the channel was SCN Ϫ ϾI Ϫ ϾCl Ϫ , and the current was inhibited by niflumic acid and DIDS in the micromolar range. In addition, we generated a sitespecific mutation (F80L) in the putative pore region of mBest3 that significantly altered the ion conduction and pharmacology of this channel. Our functional and mutational studies examining the biophysical properties of mBest3 indicate that it functions as a poreforming chloride channel that is activated by physiological levels of calcium. This study reports novel findings regarding the molecular expression, tissue localization, and functional properties of mBest3 cloned from heart.

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Section: Discussionmentioning

confidence: 61%

Expression, localization, and functional properties of Bestrophin 3 channel isolated from mouse heart

O'Driscoll¹,

Hatton²,

Burkin³

et al. 2008

American Journal of Physiology-Cell Physiology

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“…This permeability sequence corresponds to the Eisenman ''weak field strength'' lyotropic series (42), indicating that in both channels, the interaction between the permeant ion and the channel is weak, and permeability is related to the ease with which the permeant ion leaves the bulk solution and enters the channel. Our data are in general agreement with previous measurements (21,22,39).…”

Section: Comparison Of Functional Properties Between Ca-activated CL mentioning

confidence: 87%

Bestrophin-2 is a candidate calcium-activated chloride channel involved in olfactory transduction

Pifferi

Pascarella²,

Boccaccio³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

109

130

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Ca-activated Cl channels are an important component of olfactory transduction. Odor binding to olfactory receptors in the cilia of olfactory sensory neurons (OSNs) leads to an increase of intraciliary Ca concentration by Ca entry through cyclic nucleotide-gated (CNG) channels. Ca activates a Cl channel that leads to an efflux of Cl from the cilia, contributing to the amplification of the OSN depolarization. The molecular identity of this Cl channel remains elusive. Recent evidence has indicated that bestrophins are able to form Ca-activated Cl channels in heterologous systems. Here we have analyzed the expression of bestrophins in the mouse olfactory epithelium and demonstrated that only mouse bestrophin-2 (mBest2) was expressed. Single-cell RT-PCR showed that mBest2 was expressed in OSNs but not in supporting cells. Immunohistochemistry revealed that mBest2 was expressed on the cilia of OSNs, the site of olfactory transduction, and colocalized with the main CNGA2 channel subunit. Electrophysiological properties of Ca-activated Cl currents from native channels in dendritic knob͞cilia of mouse OSNs were compared with those induced by the expression of mBest2 in HEK-293 cells. We found the same anion permeability sequence, small estimated single-channel conductances, a Ca sensitivity difference of one order of magnitude, and the same side-specific blockage of the two Cl channel blockers commonly used to inhibit the odorant-induced Ca-activated Cl current in OSNs, niflumic acid, and 4-acetamido-4 -isothiocyanato-stilben-2,2 -disulfonate (SITS). Therefore, our data suggest that mBest2 is a good candidate for being a molecular component of the olfactory Ca-activated Cl channel.ion channel ͉ olfaction ͉ olfactory sensory neurons ͉ patch-clamp ͉ sensory coding

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“…This sequence is different from the sequence of their free-solution mobilities (Eisenman series I: I -> Br -> Cl -> F -) but resembles the Eisenman selectivity sequence III, indicating a moderate electrical field strength within the channel pore that now favors small, dehydrated halides for passage (25). This explained the selectivity of CLDN4 for anion over cation.…”

mentioning

confidence: 79%

Claudin-4 forms paracellular chloride channel in the kidney and requires claudin-8 for tight junction localization

Hou

Renigunta²,

Yang³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

203

233

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Tight junctions (TJs) play a key role in mediating paracellular ion reabsorption in the kidney. The paracellular pathway in the collecting duct of the kidney is a predominant route for transepithelial chloride reabsorption that determines the extracellular NaCl content and the blood pressure. However, the molecular mechanisms underlying the paracellular chloride reabsorption in the collecting duct are not understood. Here we showed that in mouse kidney collecting duct cells, claudin-4 functioned as a Cl -channel. A positively charged lysine residue at position 65 of claudin-4 was critical for its anion selectivity. Claudin-4 was observed to interact with claudin-8 using several criteria. In the collecting duct cells, the assembly of claudin-4 into TJ strands required its interaction with claudin-8. Depletion of claudin-8 resulted in the loss of paracellular chloride conductance, through a mechanism involving its recruitment of claudin-4 during TJ assembly. Together, our data show that claudin-4 interacts with claudin-8 and that their association is required for the anion-selective paracellular pathway in the collecting duct, suggesting a mechanism for coupling chloride reabsorption with sodium reabsorption in the collecting duct.C hloride is the predominant extracellular ionic constituent and thereby determines extracellular fluid volume (ECFV) and blood pressure (1-3). Although only responsible for the reabsorption of 2-3% filtered chloride, the aldosterone-sensitive distal nephron (ASDN) plays a vital regulatory role in renal handling of salt, ECFV control, and managing blood pressure (4). The ASDN comprises the distal convoluted tubule (DCT), the connecting tubule (CNT), and the collecting duct. The collecting duct is characterized by a heterogeneous epithelium-the principal cells and intercalated cells (5). Sodium reabsorption in the collecting duct is an active process driven by the basolateral Na + /K + -ATPase; acts through the apical epithelial sodium channel (ENaC) in the principal cell (6); and is responsible for generating the lumen-negative transepithelial potential. This electrogenic transport step creates a favorable electrical driving force for luminal reabsorption of chloride and secretion of potassium and proton. Chloride is transported by two major mechanisms (1). Chloride is actively reabsorbed by an electroneutral Cl − /HCO − exchanger (Slc26a4: pendrin) localized to the apical membrane of the β-type intercalated cell (7). Choride exits this cell via a basolateral Cl − channel (2) and diffuses passively down electrochemical gradients via the paracellular channel in the tight junction (TJ).The TJ is the most apical member of the junctional complex found in vertebrate epithelia responsible for the barrier to movement of ions and molecules between apical and basal compartments, the paracellular pathway (8). TJs are composed of three transmembrane proteins: occludin, claudins, and junctional adhesion molecule (JAM). The claudins (CLDNs) are a 28-member family of tetraspan proteins that range in m...

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Ionic selectivity revisited: The role of kinetic and equilibrium processes in ion permeation through channels

Cited by 528 publications

References 95 publications

Expression, localization, and functional properties of Bestrophin 3 channel isolated from mouse heart

Expression, localization, and functional properties of Bestrophin 3 channel isolated from mouse heart

Bestrophin-2 is a candidate calcium-activated chloride channel involved in olfactory transduction

Claudin-4 forms paracellular chloride channel in the kidney and requires claudin-8 for tight junction localization

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