Biomedical subjects

K Kunzelmann

Publications and source records attributed to K Kunzelmann.

93 records · Page 6Linked to original sources

PubMed1987

Characteristics of apical chloride channels in human colon cells (HT29).

Recent studies have demonstrated that active chloride secretion in mammalian colon and other epithelia, is dependent on the induction of an increase of apical chloride conductance. Since the physical characteristics of apical chloride channels in man have not been elucidated, patch clamp analysis of human colon cells (HT29), in culture, was performed, after stimulation with db-cAMP 10(-4) mol/l. In excised inside out patches of apical membranes two types of channels were found. The smaller and less frequent channel had a mean conductance of 15 +/- 1 pS (n = 9). This type of channel showed identical I/V curves in NaCl and KCl solutions. It was inhibited by a chloride channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB). The more frequently observed larger conductance channel was selective for anions and was impermeable to Na+ and K+. Regarding anion selectivity, the channel was similarly permeable to Cl-, Br-, I-, and NO3-, but was impermeable to gluconate. The channel was completely inhibited by the potent Cl- channel blocker NPPB (10(-6) mol/l). This channel exhibited rectification: The conductance was 50 +/- 4 pS at positive clamp potentials (sign referred to bath with respect to pipette interior) and 32 +/- 3 (n = 33) pS at negative voltages. Moreover, the open state probability was doubled when the clamp potential was increased from -20 to +20 mV. These results demonstrate the existence of chloride channels in the apical membrane of db-cAMP treated colonic carcinoma cells.

Chlorides↗

PubMedDate not supplied

Expression and function of colonic epithelial KvLQT1 K+ channels.

1. KvLQT1 (KCNQ1) is a voltage-gated K+ channel essential for repolarization of the heart action potential. Defects in ion channels have been demonstrated in cardiac arrhythmia. This channel is inhibited potently by the chromanol 293B. The same compound has been shown to block cAMP-dependent electrolyte secretion in rat and human colon. Therefore, it was suggested that a K+ channel similar to KvLQT1 is expressed in the colonic epithelium. 2. In the present paper, expression of KvLQT1 and its function in colonic epithelial cells is described. Reverse transcription-polymerase chain reaction analysis of rat colonic mucosa demonstrated expression of KvLQT1 in both crypt cells and surface epithelium. When expressed in Xenopus oocytes, KvLQT1 induced a typical delayed activated K+ current. 3. As demonstrated, the channel activity could be further activated by increases in intracellular cAMP. These and other data support the concept that KvLQT1 is forming a component of the basolateral cAMP-activated K+ conductance in the colonic epithelium.

1-Methyl-3-isobutylxanthine↗

PubMedDate not supplied

Defects in processing and trafficking of cystic fibrosis transmembrane conductance regulator.

In most epithelial tissues Cl(-) transport relies on the cystic fibrosis transmembrane conductance regulator (CFTR) which has dual function as a Cl(-) channel and as a regulator of other ion channels. More than 900 different mutations in the CFTR gene are the cause for defective transport of Cl(-) and Na(+) and impaired secretion or absorption of electrolytes in cystic fibrosis. However, the CFTR mutation delta F508 is the most common reason for the frequently inherited disease among the Caucasian population. Maturation and processing of delta F508-CFTR is defective which leads to expression of only very little but functional CFTR in the cell membrane. Understanding the processing and trafficking of CFTR may give a clue to the question as to how the expression and residual function of delta F508-CFTR can be enhanced, and may lead to the development of new pharmacological tools for the treatment of cystic fibrosis.

Animals↗