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

Abstract

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.