Input resistance is voltage dependent due to activation of Ih channels in rat CA1 pyramidal cells

The contribution of the hyperpolarization-activated cation current (I-h) to input resistance (R-N) and resting potential (RP) was investigated during whole-cell patch-clamp recordings in CA1 pyramidal cells of rat hippocampal slices. In current-clamp mode, R-N was determined at different membrane potentials. R-N decreased with increasing hyperpolarization, from about 260 MOmega to 140 MOmega at potentials of about -60 mV and -110 mV, respectively. Both the potential of half-maximal reduction of R-N and the potential of half-maximal I-h activation (determined in voltage-clamp mode) were approximately -90 mV. The analysis of the voltage sag indicative of I-h activation revealed a preferential activity of I-h channels in a voltage range between -70 and -95 mV. ZD7288 (50 muM), a specific I-h blocker, led to a hyperpolarization by about 4.8 mV, increased R-N by approximately 45% within a potential range between -65 and -80 mV, and abolished the voltage dependence of R-N. Gabapentin (GBP, 100 muM), an I-h channel agonist, led to a depolarization by about 2.4 mV and reduced R-N by about 20% within a potential range between -65 and -80 mV. In conclusion, our data show that R-N is voltage dependent due to I-h channel activation and that I-h channels are preferentially active at voltages between -70 and -95 mV. Furthermore, we demonstrated that R-N can be modulated by antiepileptic drugs such as GBP, which may partly explain its antiepileptic effect as due to decreasing the sensitivity to excitatory input. (C) 2004 Wiley-Liss, Inc.