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Human ClCa1 modulates anionic conduction of calcium-dependent chloride currents.

Hamann M, Gibson A, Davies N, Jowett A, Walhin JP, Partington L, Affleck K, Trezise D, Main M - J. Physiol. (Lond.) (2009)

Bottom Line: We further show that hClCa1 does not modify the permeability sequence but increases the Cl- conductance while decreasing the G(SCN-)/G(Cl-) conductance ratio from approximately 2-3 to approximately 1.We use an Eyring rate theory (two barriers, one site channel) model and show that the effect of hClCa1 on the anionic channel can be simulated by its action on lowering the first and the second energy barriers.Rather, hClCa1 elevates the single channel conductance of endogenous Ca(2+)-dependent Cl- channels by lowering the energy barriers for ion translocation through the pore.

View Article: PubMed Central - PubMed

Affiliation: Leicester University, Department of Cell Physiology and Pharmacology, Medical Sciences Building, PO Box 138, University Road, Leicester LE1 9HN, UK. mh86@le.ac.uk

ABSTRACT
Proteins of the CLCA gene family including the human ClCa1 (hClCa1) have been suggested to constitute a new family of chloride channels mediating Ca(2+)-dependent Cl- currents. The present study examines the relationship between the hClCa1 protein and Ca(2+)-dependent Cl- currents using heterologous expression of hClCa1 in HEK293 and NCIH522 cell lines and whole cell recordings. By contrast to previous reports claiming the absence of Cl- currents in HEK293 cells, we find that HEK293 and NCIH522 cell lines express constitutive Ca(2+)-dependent Cl- currents and show that hClCa1 increases the amplitude of Ca(2+)-dependent Cl- currents in those cells. We further show that hClCa1 does not modify the permeability sequence but increases the Cl- conductance while decreasing the G(SCN-)/G(Cl-) conductance ratio from approximately 2-3 to approximately 1. We use an Eyring rate theory (two barriers, one site channel) model and show that the effect of hClCa1 on the anionic channel can be simulated by its action on lowering the first and the second energy barriers. We conclude that hClCa1 does not form Ca(2+)-dependent Cl- channels per se or enhance the trafficking/insertion of constitutive channels in the HEK293 and NCIH522 expression systems. Rather, hClCa1 elevates the single channel conductance of endogenous Ca(2+)-dependent Cl- channels by lowering the energy barriers for ion translocation through the pore.

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Scheme 1
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fig09: Scheme 1

Mentions: To calculate the rates, we used a rate theory model (Glässtone et al. 1941; Davies et al. 1996) in which the channel has two energy barriers and a single well or binding site able to accommodate a monovalent anion. For simplicity we distributed the barriers and binding site equally within the voltage field (see Scheme 1).


Human ClCa1 modulates anionic conduction of calcium-dependent chloride currents.

Hamann M, Gibson A, Davies N, Jowett A, Walhin JP, Partington L, Affleck K, Trezise D, Main M - J. Physiol. (Lond.) (2009)

Scheme 1
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2691903&req=5

fig09: Scheme 1
Mentions: To calculate the rates, we used a rate theory model (Glässtone et al. 1941; Davies et al. 1996) in which the channel has two energy barriers and a single well or binding site able to accommodate a monovalent anion. For simplicity we distributed the barriers and binding site equally within the voltage field (see Scheme 1).

Bottom Line: We further show that hClCa1 does not modify the permeability sequence but increases the Cl- conductance while decreasing the G(SCN-)/G(Cl-) conductance ratio from approximately 2-3 to approximately 1.We use an Eyring rate theory (two barriers, one site channel) model and show that the effect of hClCa1 on the anionic channel can be simulated by its action on lowering the first and the second energy barriers.Rather, hClCa1 elevates the single channel conductance of endogenous Ca(2+)-dependent Cl- channels by lowering the energy barriers for ion translocation through the pore.

View Article: PubMed Central - PubMed

Affiliation: Leicester University, Department of Cell Physiology and Pharmacology, Medical Sciences Building, PO Box 138, University Road, Leicester LE1 9HN, UK. mh86@le.ac.uk

ABSTRACT
Proteins of the CLCA gene family including the human ClCa1 (hClCa1) have been suggested to constitute a new family of chloride channels mediating Ca(2+)-dependent Cl- currents. The present study examines the relationship between the hClCa1 protein and Ca(2+)-dependent Cl- currents using heterologous expression of hClCa1 in HEK293 and NCIH522 cell lines and whole cell recordings. By contrast to previous reports claiming the absence of Cl- currents in HEK293 cells, we find that HEK293 and NCIH522 cell lines express constitutive Ca(2+)-dependent Cl- currents and show that hClCa1 increases the amplitude of Ca(2+)-dependent Cl- currents in those cells. We further show that hClCa1 does not modify the permeability sequence but increases the Cl- conductance while decreasing the G(SCN-)/G(Cl-) conductance ratio from approximately 2-3 to approximately 1. We use an Eyring rate theory (two barriers, one site channel) model and show that the effect of hClCa1 on the anionic channel can be simulated by its action on lowering the first and the second energy barriers. We conclude that hClCa1 does not form Ca(2+)-dependent Cl- channels per se or enhance the trafficking/insertion of constitutive channels in the HEK293 and NCIH522 expression systems. Rather, hClCa1 elevates the single channel conductance of endogenous Ca(2+)-dependent Cl- channels by lowering the energy barriers for ion translocation through the pore.

Show MeSH
Related in: MedlinePlus