cAMP activation of apical membrane Cl- channels: Theoretical considerations for impedance analysis

Transepithelial electrical impedance analysis provides a sensitive method t o evaluate the conductances and capacitances of apical and basolateral plas ma membranes of epithelial cells. Impedance analysis is complicated, due no t only to the anatomical arrangement of the cells and their paracellular sh unt pathways, but also in particular to the existence of audio frequency-de pendent capacitances or dispersions. In this paper we explore implications and consequences of anatomically related Maxwell-Wagner and Cole-Cole diele ctric dispersions that impose limitations, approximations, and pitfalls of impedance analysis when tissues are studied under widely ranging spontaneou s rates of transport, and in particular when apical membrane sodium and chl oride channels are activated by adenosine 3',5'-cyclic monophosphate (CAMP) in A6 epithelia. We develop the thesis that capacitive relaxation processe s of any origin lead not only to dependence on frequency of the impedance l ocus, but also to the appearance of depressed semicircles in Nyquist transe pithelial impedance plots, regardless of the tightness or leakiness of the paracellular shunt pathways. Frequency dependence of capacitance precludes analysis of data in traditional ways, where capacitance is assumed constant , and is especially important when apical and/or basolateral membranes exhi bit one or more dielectric dispersions.