Short-circuit current overshoot in epithelial sodium channels following apical sodium jump.
Following a jump in the sodium concentration of the solution bathing the apical surface of frog skin, the inward sodium current rises rapidly to a peak and then falls to a steady-state plateau. Lindemann suggested that this fall is due to rapid closing (in 2 to 3 s) of Na channels. However, the lack of a corresponding corner frequency in the sodium-noise spectrum indicates a much slower closing. We propose a compartmental mechanism for the overshoot: the inward Na current causes Na to accumulate in the intracellular region adjacent to the sodium channel--a virtual compartment--thereby decreasing the outside/inside [Na] ratio. As that ratio falls with rising [Na] in the virtual compartment, the force driving the current falls. The predictions of such a model have been curve-fitted to the time-course of the current overshoot. The differential equation describing the rate of change of [Na] in the virtual compartment has several time constants: a filling time for the compartment, a leakage time for escape of Na into the larger intracellular space, a mixing time in the apical bathing solution, and, of course, the channel-closing time. This curve fitting shows that channel closing becomes important only in the tail of the overshoot (> 15 s) with mean open times in a range from 7 s to 3 min. Similarly, the time-course of the current after washout of apical [Na] was fitted using the same differential equation, with the channel-closing time replaced with a channel-opening time. Other phenomena explainable by this compartmental model but not by fast channel closing include the open-circuit-potential overshoot, current overshoot through nystatin channels, and the less-than-59-mV-per-decade slopes of semilog plots of open-circuit potential vs. [Na].
Machlup
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S
Department of Physics, Case Western Reserve University, Cleveland, OH 44106.
Hoshiko
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T
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004563:Electrochemistry; D004848:Epithelium / Q000378:metabolism; D066298:In Vitro Techniques; D008433:Mathematics; D011894:Rana pipiens; D012964:Sodium / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*
D015222:Sodium Channels; D012964:Sodium