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Regulation of Na⁺ channels by luminal Na⁺ in rat cortical collecting tubule

Lawrence G. Palmer, Henry Sackin and Gustavo Frindt

1. The idea that luminal Na⁺ can regulate epithelial Na⁺ channels was tested in the cortical collecting tubule of the rat using whole-cell and single-channel recordings. Here we report results consistent with the idea of Na⁺ self-inhibition.

2. Macroscopic amiloride-sensitive currents (I_Na) were measured by conventional whole-cell clamp. I_Na was a saturable function of external Na⁺ concentration ([Na⁺]_o) with an apparent K_m of 9 mM. Single channel currents (i_Na) were measured in cell-attached patches. i_Na increased with pipette Na⁺ concentration with an apparent K_m of 48 mM. Since I_Na = (i_Na)NP_o, the different K_m values imply that the channel density (N) and/or open probability (P_o) increase as [Na⁺]_o decreases. Reduction of [Na⁺]_o after increasing intracellular Na⁺ concentration also increased the outward amiloride-sensitive conductance, consistent with activation of the Na⁺ channels.

3. The underlying mechanism was studied by changing pipette Na⁺ concentration while recording from cell-attached patches. No increase in NP_o was observed, suggesting that the effect is not a direct interaction between [Na⁺]_o and the channel.

4. [Na⁺]_o was varied outside the patch-clamp pipette while recording from cell-attached patches. When amiloride was in the bath to prevent Na⁺ entry, no change in NP_o was observed.

5. Activation of the channels by hyperpolarization was observed with 140 mM Na⁺_o but not with 14 mM Na⁺_o.

6. The results are consistent with the concept of self-inhibition of Na⁺ channels by luminal Na⁺. Activation of the channels by lowering [Na⁺]_o is not additive with that achieved by hyperpolarization.

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