PROPERTIES OF EPITHELIAL POTASSIUM CHANNELS

  • Dawson, David (PI)

Project: Research project

Project Details

Description

The potassium content of human body fluids is regulated by virtue of
epithelial transport processes in the colon and distal renal tubule which
lead to the absorption or secretion of this ion. Understanding the
mechanisms of potassium transport, and in particular the control of these
processes by drugs and hormones, requires a detailed description of the
properties of the ion pumps and ion channels in the apical and basolateral
membranes of the transporting cells. Despite the obvious importance of
epithelial potassium channels the properties of these transport elements
have not been studied in detail because the series arrangement of apical
and basolateral membranes precludes the direct measurement of isotope flows
and electrical currents through the channels. We have developed a unique
preparation of the isolated turtle colon in which the basolateral membrane
is functionally isolated by using the polyene antibiotic, amphotericin-B,
to modify the cation selectivity and conductance of the apical membrane.
This preparation has permitted us for the first time to measure
simultaneously the potassium current and tracer flows through the channel.
Our initial studies revealed that the channel is permeable to at least
three cations, potassium, challium and rubidium, and more importantly that
these ions interact in a manner consistent with a single-file mechanism of
ion flow. The ionic interactions are revealed in the form of positive
coupling between the flows of permeant ions (knock effects) and reductions
in ionic permeability of a test ion when a second ion is added (block
effects). In addition we have shown that the divalent cation, barium, is a
potent blocker of the channel as is quinidine, a blocker of the
calcium-induced potassium conductance in human red blood cells. The object
of the propoed research is to obtain, for the firt time, a detailed
analysis of the mechanism of ion translocation through an epitelial
potassium channel. We will determine the kinetics of single ion flows and
determine the flux-ratios for K, T1 and Rb. We will study in detail the
nature of cation-cation interactions which occur in the channel and
investigate possible sideness or asymmetry between the cellular and
extracellular aspects of the channel. We will attempt to determine if
protons or water pass through the channel, and investigate the action of
blociers; barium or quinidine.
StatusFinished
Effective start/end date8/1/837/31/86

Funding

  • National Institutes of Health

ASJC

  • Medicine(all)

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