The effects of rises in external K(+) (K(ext)) on I(h) were investigated in CA1 pyramidal cells of rat hippocampal slices using the whole-cell patch clamp technique. At the basal K(ext) level (2.5 mM), hyperpolarization-activated cation current (I(h)) had a maximal amplitude of -350+/-60 pA which was enhanced by approximately 60 and approximately 95% at 5 and 7.5 mM K(ext), respectively. The midpoint activation voltage was significantly shifted from -80 mV in the negative direction to about -87 mV at both 5 and 7.5 mM K(ext), without appreciable alterations of the current kinetics. The maximal conductance was approximately 2.4 nS under control conditions and significantly increased to approximately 3.3 and approximately 5.6 nS at 5 and 7.5 mM K(ext), respectively. The reversal potential was shifted in the positive direction, from a control value of approximately -30 mV by approximately 6 and approximately 14 mV at 5 and 7.5 mM K(ext), respectively. Our data demonstrate that even moderate changes in K(ext) have a substantial effect on the properties of I(h).
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