TY - JOUR

T1 - Mitochondria-Rich Cells as Experimental Model in Studies of Epithelial Chloride Channels

AU - Willumsen, Niels J.

AU - Amstrup, Jan

AU - Møbjerg, Nadja

AU - Jespersen, Åse

AU - Kristensen, Poul

AU - Larsen, Erik Hviid

N1 - Author Keywords: Bufo bufo; Mitochondria-rich cell; Voltage-activated Cl- channel; ß-Adrenergic receptor; Cyclic AMP; CFTR; Patch clamp; Noise analysis; Cytochalasin D; Actin

PY - 2002

Y1 - 2002

N2 - The mitochondria-rich (mr) cell of amphibian skin epithelium is differentiated as a highly specialised pathway for passive transepithelial transport of chloride. The apical membrane of mr cells expresses several types of Cl- channels, of which the function of only two types has been studied in detail. (i) One type of channel is gated by voltage and external chloride concentration. This intriguing type of regulation leads to opening of channels only if [Cl-]o is in the millimolar range and if the electrical potential is of a polarity that secures an inwardly directed net flux of this ion. Reversible voltage activations of the conductance proceed with long time constants, which depend on V in such a way that the rate of conductance activation increases when V is clamped at more negative values (serosal bath grounded). The gating seems to involve processes that are dependent on F-actin localised in the submembrane domain in the neck region of the flask-shaped mr cell. (ii) The other identified Cl- pathway of mr cells is mediated by small-conductance apical CFTR chloride channels as concluded from its activation via ß-adrenergic receptors, ion selectivity, genistein stimulation and inhibition by glibenclamide. bbCFTR has been cloned, and immunostaining has shown that the gene product is selectively expressed in mr cells. There is cross-talk between the two pathways in the sense that activation of the conductance of the mr cell by voltage clamping excludes activation via receptor occupation, and vice versa. The mechanism of this cross-talk is unknown.

AB - The mitochondria-rich (mr) cell of amphibian skin epithelium is differentiated as a highly specialised pathway for passive transepithelial transport of chloride. The apical membrane of mr cells expresses several types of Cl- channels, of which the function of only two types has been studied in detail. (i) One type of channel is gated by voltage and external chloride concentration. This intriguing type of regulation leads to opening of channels only if [Cl-]o is in the millimolar range and if the electrical potential is of a polarity that secures an inwardly directed net flux of this ion. Reversible voltage activations of the conductance proceed with long time constants, which depend on V in such a way that the rate of conductance activation increases when V is clamped at more negative values (serosal bath grounded). The gating seems to involve processes that are dependent on F-actin localised in the submembrane domain in the neck region of the flask-shaped mr cell. (ii) The other identified Cl- pathway of mr cells is mediated by small-conductance apical CFTR chloride channels as concluded from its activation via ß-adrenergic receptors, ion selectivity, genistein stimulation and inhibition by glibenclamide. bbCFTR has been cloned, and immunostaining has shown that the gene product is selectively expressed in mr cells. There is cross-talk between the two pathways in the sense that activation of the conductance of the mr cell by voltage clamping excludes activation via receptor occupation, and vice versa. The mechanism of this cross-talk is unknown.

U2 - 10.1016/S0005-2736(02)00591-6

DO - 10.1016/S0005-2736(02)00591-6

M3 - Journal article

VL - 1566

SP - 28

EP - 43

JO - B B A - General Subjects

JF - B B A - General Subjects

SN - 0304-4165

IS - 1-2

ER -