This review focused on results obtained with methods that allow studies of ionic channels in situ, namely, patch clamping and current-noise analysis. We reported findings for ionic channels in apical and basolateral plasma membranes of various tight and leaky epithelia from a wide range of animal species and tissues. As for ionic channel "species," we restricted ourselves to the discussion of cation-specific (Na+ or K+), hybrid (Na+ and K+), and Cl- channels. For the K+-specific channels it can be said that their properties in conduction (multisite, single file), selectivity (only "K+-like" cations), and blocking behavior (Ba2+, Cs+, TEA) much resemble those observed for K+ channels in excitable membranes. This seems to include also the Ca2+-activated "maxi" K+ channel. Thus, K+ channels in excitable membranes and K+ channels in epithelia appear to be very closely related in their basic structural principles. This is, however, not at all unexpected, because K+ channels provide the dominant permeability characteristics of nearly all plasma membranes from symmetrical and epithelial cells. An exception is, of course, apical membranes of tight epithelia whose duty is Na+ absorption against large electrochemical gradients in a usually anisosmotic environment. Here, Na+ channels dominate, although a minor fraction of membrane permeability comes from K+ channels, as in frog skin, colon, or distal nephron. Epithelial Na+ channels are different from excitable Na+ channels in that they 1) are far more selective and 2) seem to be chemically rather than electrically gated. Furthermore, their specific blockers belong to very different chemical families, although a guanidinium/amidinium moiety is a common feature (TTX vs. amiloride). [For a more detailed summary of Na+ channel properties see sect. IV H.] Most interesting is the occurrence of relatively nonselective cationic (hybrid) channels in apical membranes of tight epithelia, like larval or adult frog skin. Here, not only the weak selectivity is astonishing but also the fact that these channels react with so-called K+-channel-specific (Ba2+, TEA) as well as with Na+-channel-specific (amiloride, BIG) compounds. Moreover, this cross-reactivity does not seem to be inhibitory but, on the contrary, stimulating. Clearly these channels may become a fascinating object with which to assess whether Na+ and K+ channels are not only structurally but also genetically related and whether they can somehow be converted into each other.(ABSTRACT TRUNCATED AT 400 WORDS)

The reaction of abdominal skins of the frog species Rana temporaria on mucosal K+-containing solutions was studied in an Ussing-type chamber by recording transepithelial potential difference (PD), short-circuit current (SCC) and conductance (G). With Na-Ringer's as serosal medium, a linear correlation between PD and the logarithm of the mucosal K+-concentration ([K]o) was obtained. The K+-dependent SCC saturated with increasing [K]o, and could quickly and reversibly be depressed by addition of Rb+, Cs+, and H+. Li+, Na+, and NH4+ did not influence K+ current. A large scatter was obtained for kinetic parameters like the slope of the PD-log[K]o-line (18--36.5 mV/decade), the apparent Michaelis constant (13--200 mM), and the maximal current of the saturable SCC (6--50 microa . cm-2), as well as for the degree of inhibition by Cs+ ions. This seemed to be caused by a time-dependent change during long time exposure to high [K]o (more than 30 sec), thereby inducing a selectivity loss of K+-transporting structures, together with an increase in SCC and G and a decrease in PD. Short time exposure to K+-containing solutions showed a competitive inhibition of K+ current by Cs+ ions, and a Michaelis constant of 6.6 mM for the inhibitory action of Cs+. Proton titration resulted in a decrease of K+ current at pH less than 3. An acidic membrane component (apparent dissociation constant 2.5 x 10(-3) M) is virtually controlling K+ transfer. Reducing the transepithelial K+-concentration gradient by raising the serosal potassium concentration was accompanied by the disappearance of SCC and PD.

We studied the influence of mucosal Ba2+ ions on the recently described (Zeiske & Van Driessche, 1979a, J. Membrane Biol. 47:77) transepithelial, mucosa towards serosa directed K+ transport in the skin of Rana temporaria. The transport parameters G (conductance), PD (potential difference), Isc (short-circuit current, "K+ current"), as well as the noise of Isc were recorded. Addition of millimolar concentrations of Ba/+ to the mucosal K+-containing solution resulted in a sudden but quickly reversible drop in Isc. G and Isc decreased continuously with increasing Ba2+ concentration, (Ba2+)o. The apparent Michaelis constant of the inhibition by Ba2+ lies within the range 40-80 microM. The apical membrane seems to remain permselective for K+ up to 500 microM (Ba2+)o. Higher (Ba2+)o, however, appears to induce a shunt (PD falls, G increases). This finding made an accurate determination of the nature of the inhibition difficult but our results tend to suggest a K+-channel block by K+-Ba2+ competition. In the presence of Ba2+, the power spectrum of the K+ current shows a second Lorentzian component in the low-frequency range, in addition to the high-frequency Lorentzian caused by spontaneous K+-channel fluctuations (Van Driessche & Zeiske, 1980). Both Lorentzian components are only present with mucosal K+ and can be depressed by addition of Cs+ ions, thus indicating that Ba2+ ions induce K+-channel fluctuations. The dependence of the parameters of the induced Lorentzian on (Ba2+)o shows arise in the plateau values to a maximum around 60 microM (Ba2+)o, followed by a sharp and progressive decrease to very low values. The corner frequency which reflects the rate of the Ba2+-induced fluctuations, however, increases quasi-linearly up to 1 mM (Ba2+)o with a tendency to saturate at higher (Ba2+)o. Based on a three-state model for the K+ channel (having one open state, one closed by the spontaneous fluctuation and one blocked by Ba2+) computer calculations compared favorably with our results. The effect of Ba2+ could be explained by assuming reversible binding at the outer side of the apical K+ channel, thereby blocking the open channel in ;competition with K+. The association-dissociation of Ba2+ at its receptor site is thought to cause a chopping of the K+ current, resulting in modulated current fluctuations.

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