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.
Surges
Rainer
R
Department of Neurology, Section of Clinical Neuropharmacology, Neurocenter, University of Freiburg, Freiburg, Germany. surges@nz.ukl.uni-freiburg.de
Freiman
Thomas M
TM
Feuerstein
Thomas J
TJ
D015761:4-Aminopyridine / Q000494:pharmacology; D000085:Acetates / Q000494:pharmacology; D000588:Amines; D000818:Animals; D000831:Animals, Newborn; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003509:Cyclohexanecarboxylic Acids; D004307:Dose-Response Relationship, Radiation; D017097:Electric Impedance; D004558:Electric Stimulation; D000077206:Gabapentin; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D008564:Membrane Potentials / Q000187:drug effects / Q000528:radiation effects; D009532:Nickel / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D026902:Potassium Channel Blockers / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D002121:Calcium Channel Blockers; D003509:Cyclohexanecarboxylic Acids; D007473:Ion Channels; D026902:Potassium Channel Blockers; D011743:Pyrimidines; C082246:ICI D2788; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D009532:Nickel; D015761:4-Aminopyridine