Sodium sensitivity of K_Na channels in mouse CA1 neurons

Potassium channels play an important role regulating transmembrane electrical activity in essentially all cell types. We were especially interested in those that determine the intrinsic electrical properties of mammalian central neurons. Over 30 different potassium channels have been molecularly identified in brain neurons, but there often is not a clear distinction between molecular structure and the function of a particular channel in the cell. Using patch-clamp methods to search for single potassium channels in excised inside-out (ISO) somatic patches with symmetrical potassium, we found that nearly all patches contained non-voltage-inactivating channels with a single-channel conductance of 100-200 pS. This conductance range is consistent with the family of sodium-activated potassium channels (Slo2.1, Slo2.2, or collectively, K_Na). The activity of these channels was positively correlated with a low cytoplasmic Na⁺ concentration (2-20 mM). Cell-attached recordings from intact neurons, however, showed little or no activity of this K⁺ channel. Attempts to increase channel activity by increasing intracellular sodium concentration ([Na⁺]_i) with bursts of action potentials or direct perfusion of Na⁺ through a whole cell pipette had little effect on K_Na channel activity. Furthermore, excised outside-out (OSO) patches across a range of intracellular [Na⁺] showed less channel activity than we had seen with excised ISO patches. Blocking the Na⁺/K⁺ pump with ouabain increased the activity of the K_Na channels in excised OSO patches to levels comparable with ISO-excised patches. Our results suggest that despite their apparent high levels of expression, the activity of somatic K_Na channels is tightly regulated by the activity of the Na⁺/K⁺ pump.NEW & NOTEWORTHY We studied K_Na channels in mouse hippocampal CA1 neurons. Excised inside-out patches showed the channels to be prevalent and active in most patches in the presence of Na⁺. Cell-attached recordings from intact neurons, however, showed little channel activity. Increasing cytoplasmic sodium in intact cells showed a small effect on channel activity compared with that seen in inside-out excised patches. Blockade of the Na⁺/K⁺ pump with ouabain, however, restored the activity of the channels to that seen in inside-out patches.