Sensitivity to flow of intrinsic gating in inwardly rectifying potassium channel from mammalian skeletal muscle.

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Abstract
1. Current through inwardly rectifying K+ channels was measured in inside-out patches from rat and human sarcolemmal vesicles and from dispersed rat flexor digitorum brevis muscle fibres. The patches were positioned so as to face the aperture of a large-diameter pipette from which solution of the same composition as the bath solution coudl be ejected. The solution within the patch pipette and the bath solution both contained principally 140 mM-KCl. 2. The kinetic behaviour of the inwardly rectifying channel was found to vary according to whether the patch was in static or flowing solution. At negative holding potentials, when the channel is open most of the time in static solution, flow produced a reversible and repeatble decrease in open probability. 3. In Mg2+-free solution the inwardly rectifying channel allows outward current to pass at positive holding potentials. This allows the kinetic behaviour of the channel in static and flowing solution to be compared over a wider voltage range. 4. In both static and flowing solution, the open probability-voltage relation is sigmoidal and can be fitted by a Boltzmann curve. As a result of flow, the maximum open probability at negative potentials is decreased and the mid-point of the relation is shifted to the right by more than 20 mV. 5. No evidence could be found for the existence of a local concentration gradient sensitive to flow. Application of suction to the patch pipette showed the inwardly rectifying channels not to be sensitive to membrane stretch. The possibility is contemplated that shear stress upon the inner face of the patch modulates the kinetic behaviour of the channel. 6. In contrast to the inwardly rectifying K+ channel, neither the Ca2+-activated K+ channel nor the ATP-regulated K+ channel are sensitive to flow.