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Studies of sodium channels in rabbit urinary bladder by noise analysis

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Summary

Sodium channels in rabbit urinary bladder were studied by noise analysis. There are two components of short-circuit current (I sc) and correspondingly two components of apical Na+ entry, one amiloride-sensitive (termedI A and the A channel, respectively) and one amiloride-insensitive (I L and the leak pathway, respectively). The leak pathway gives rise tol/f noise, while the A channel in the presence of amiloride gives rise to Lorentzian noise. A two-state model of the A channel accounts well for how the corner frequency and plateau value of Lorentzian noise vary with amiloride concentration. The single-channel current is 0.64 pA, and the conducting channel density is on the order of 40 copies per cell. Triamterene blocks the A channel alone, and increasing external Na+ decreases the number but not the single-channel permeability of the A channel. Hydrostatic pressure pulses (“punching”) increase the number of both pathways. Repeated washing of the mucosal surface removes most of the leak pathway without affecting the A channel.

Properties of the A channel revealed by noise analysis of various tight epithelia are compared, and the mechanism ofl/f noise is discussed. It is suggested that the A channel is synthesized intracellularly, stored in intracellular vesicles, transferred with or from vesicular membrane into apical membrane under the action of microfilaments, and degraded into the leak pathway, which is washed out into urine or destroyed. The A channel starts withP Na/P K∼30 and loses selectivity in stages untilP Na/P K reaches the free-solution mobility ratio (∼0.7) for the leak pathway. This turnover cycle functions as a mechanism of repair and regulation for Na+ channels, analogous to the repair and regulation of most intracellular proteins by turnover. Vesicular delivery of membrane channels may be operating in several other epithelia.

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Lewis, S.A., Ifshin, M.S., Loo, D.D.F. et al. Studies of sodium channels in rabbit urinary bladder by noise analysis. J. Membrain Biol. 80, 135–151 (1984). https://doi.org/10.1007/BF01868770

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