POLARIZED ION-TRANSPORT DURING MIGRATION OF TRANSFORMED MADIN-DARBY CANINE KIDNEY-CELLS

Epithelial cells lose their usual polarization during carcinogenesis. Although most malignant tumours are of epithelial origin little is kno wn about ion channels in carcinoma cells. Previously, we observed that migration of transformed Madin-Darby canine kidney (MDCK-F) cells dep ended on oscillating K+ channel activity. In the present study we exam ined whether periodic K+ channel activity may cause changes of cell vo lume, and whether K+ channel activity is distributed in a uniform way in MDCK-F cells. After determining the average volume of MDCK-F cells (2013+/-270 mu m(3); n=8) by means of atomic force microscopy we deduc ed volume changes by calculating the K+ efflux during bursts of K+ cha nnel activity. Therefore, we measured the membrane conductance of MDCK -F cells which periodically rose by 22.3+/-2.5 nS from a resting level of 6.5+/-1.4 nS (n=12), and we measured the membrane potential which hyperpolarized in parallel from -35.4+/-1.2 mV to -71.6+/-1.8 mV (n=11 ). The distribution of K+ channel activity was assessed by locally sup erfusing the front or rear end of migrating MDCK-F cells with the K+ c hannel blocker charybdotoxin (CTX). Only exposure of the rear end to C TX inhibited migration providing evidence for ''horizontal'' polarizat ion of K+ channel activity in transformed MDCK-F cells. This is in con trast to the ''vertical'' polarization in parent MDCK cells. We propos e that the asymmetrical distribution of K+ channel activity is a prere quisite for migration of MDCK-F cells.