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 microM), 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 microM), 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.