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.
Copyright 2004 Wiley-Liss, Inc.