Input resistance is voltage dependent due to activation of Ih channels in rat CA1 pyramidal cells
✍ Scribed by Rainer Surges; Thomas M. Freiman; Thomas J. Feuerstein
- Book ID
- 102906767
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 869 KB
- Volume
- 76
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
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. © 2004 Wiley‐Liss, Inc.