Cytosolic potassium controls CFTR deactivation in human sweat duct

Reddy, M. M.; Quinton, Paul M.

doi:10.1152/ajpcell.00134.2005

Cited by 28 publications

(17 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…other native tissues, the sweat gland reinforces the lesson that CFTR functions in a pivotal role to couple transport activity with transport capacity and cell energy supply on a moment-to-moment basis (113,123,124,133,137).…”

Section: Cftr and Phosphatases Lesson 12: Cftr Clconductance Is Deacmentioning

confidence: 63%

Cystic Fibrosis: Lessons from the Sweat Gland

2007

View full text Add to dashboard Cite

Lessons from the sweat gland on cystic fibrosis (CF) began long before modern medicine became a science. In European folklore, the curse that "a child that taste salty when kissed will soon die" (Alonso y de los Ruyzes de Fonteca J. Diez Previlegios para Mugeres Prenadas. Henares, Spain, 1606) has been taken by many as a direct reference to cystic fibrosis [Busch R. Acta Univ Carol Med (Praha) 36: 13-15, 1990]. The high salt concentration in sweat from patients with CF is now accepted as almost pathognomonic with this fatal genetic disease, but the earliest descriptions of cystic fibrosis as a disease entity did not mention sweat or sweat glands (Andersen DH. Am J Dis Child 56: 344-399, 1938; Andersen DH, Hodges RG. Am J Dis Child 72: 62-80, 1946). Nonetheless, defective sweating soon became an inseparable, and major, component of the constellation of symptoms that diagnose "cystic fibrosis" (Davis PB. Am J Respir Crit Care Med 173: 475-482, 2006). The sweat gland has played a foremost role in diagnosing, defining pathophysiology, debunking misconceptions, and increasing our understanding of the effects of the disease on organs, tissues, cells, and molecules. The sweat gland has taught us much.

show abstract

Section: Cftr and Phosphatases Lesson 12: Cftr Clconductance Is Deacmentioning

confidence: 63%

Cystic Fibrosis: Lessons from the Sweat Gland

2007

View full text Add to dashboard Cite

show abstract

“…3, and ). After wash‐out of high [K + ], the V m returned to baseline with an undershoot that was consistent with the activation of the Na + –K + pump when the extracellular [K + ] is elevated (Reddy & Quinton, 1991, 2006).…”

mentioning

confidence: 55%

Iontophoretic β‐adrenergic stimulation of human sweat glands: possible assay for cystic fibrosis transmembrane conductance regulator activity in vivo

Shamsuddin¹,

Reddy²,

Quinton³

2008

Experimental Physiology

Self Cite

View full text Add to dashboard Cite

With the advent of numerous candidate drugs for therapy in cystic fibrosis (CF), there is an urgent need for easily interpretable assays for testing their therapeutic value. Defects in the cystic fibrosis transmembrane conductance regulator (CFTR) abolished β-adrenergic but not cholinergic sweating in CF. Therefore, the β-adrenergic response of the sweat gland may serve both as an in vivo diagnostic tool for CF and as a quantitative assay for testing the efficacy of new drugs designed to restore CFTR function in CF. Hence, with the objective of defining optimal conditions for stimulating β-adrenergic sweating, we have investigated the components and pharmacology of sweat secretion using cell cultures and intact sweat glands. We studied the electrical responses and ionic mechanisms involved in β-adrenergic and cholinergic sweating. We also tested the efficacy of different β-adrenergic agonists. Our results indicated that in normal subjects the cholinergic secretory response is mediated by activation of Ca 2+ -dependent Cl − conductance as well as K + conductances. In contrast, the β-adrenergic secretory response is mediated exclusively by activation of a cAMP-dependent CFTR Cl − conductance without a concurrent activation of a K + conductance. Thus, the electrochemical driving forces generated by β-adrenergic agonists are significantly smaller compared with those generated by cholinergic agonists, which in turn reflects in smaller β-adrenergic secretory responses compared with cholinergic secretory responses. Furthermore, the β-adrenergic agonists, isoproprenaline and salbutamol, induced sweat secretion only when applied in combination with an adenylyl cyclase activator (forskolin) or a phosphodiesterase inhibitor (3-isobutyl-1-methylxanthine, aminophylline or theophylline). We surmise that to obtain consistent β-adrenergic sweat responses, levels of intracellular cAMP above that achievable with a β-adrenergic agonist alone are essential. β-Adrenergic secretion can be stimulated in vivo by concurrent iontophoresis of these drugs in normal, but not in CF, subjects.

show abstract

“…As a general example of this type of regulation, it has recently been shown that declining intracellular potassium deactivates via dephosphorylation the cystic fibrosis transmembrane conductance regulator (CFTR) Cl -channel limiting the apical influx of Cl -and Na + until the intracellular concentration of potassium is stabilized [67]. In regards to AVD and apoptosis, cultured cortical neurons treated with staurosporine or ceramide resulted in an inhibition of chloride currents preventing apoptotic cell shrinkage.…”

Section: Potassium As a Signal For Apoptosismentioning

confidence: 99%

Cell shrinkage and monovalent cation fluxes: Role in apoptosis

Bortner

Cidlowski

2007

Archives of Biochemistry and Biophysics

230

193

View full text Add to dashboard Cite

The loss of cell volume or cell shrinkage has been a morphological hallmark of the programmed cell death process known as apoptosis. This isotonic loss of cell volume has recently been term apoptotic volume decrease or AVD to distinguish it from inherent volume regulatory responses that occurs in cells under anisotonic conditions. Recent studies examining the intracellular signaling pathways that result in this unique cellular characteristic have determined that a fundamental movement of ions, particularly monovalent ions, underlie the AVD process and plays an important role on controlling the cell death process. An efflux of intracellular potassium was shown to be a critical aspect of the AVD process, as preventing this ion loss could protect cells from apoptosis. However, potassium plays a complex role as a loss of intracellular potassium has also been shown to be beneficial to the health of the cell. Additionally, the mechanisms that a cell employs to achieve this loss of intracellular potassium vary depending on the cell type and stimulus used to induce apoptosis, suggesting multiple ways exist to accomplish the same goal of AVD. Additionally, sodium and chloride have been shown to play a vital role during cell death in both the signaling and control of AVD in various apoptotic model systems. This review examines the relationship between this morphological change and intracellular monovalent ions during apoptosis.

show abstract

Cytosolic potassium controls CFTR deactivation in human sweat duct

Abstract: Reddy, M. M., and P. M. Quinton. Cytosolic potassium controls CFTR deactivation in human sweat duct.

Cited by 28 publications

References 36 publications

Cystic Fibrosis: Lessons from the Sweat Gland

Cystic Fibrosis: Lessons from the Sweat Gland

Iontophoretic β‐adrenergic stimulation of human sweat glands: possible assay for cystic fibrosis transmembrane conductance regulator activity in vivo

Cell shrinkage and monovalent cation fluxes: Role in apoptosis

Contact Info

Product

Resources

About