Input resistance is voltage dependent due to activation of I h 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 MΩ to 140 MΩ 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 μM), 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 μM), 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. © 2004 Wiley‐Liss, Inc.