Pflügers Archiv

, Volume 435, Issue 1, pp 99–106

Action of the hyperpolarization-activated current (Ih) blocker ZD 7288 in hippocampal CA1 neurons

  • S. Gasparini
  • D. DiFrancesco

DOI: 10.1007/s004240050488

Cite this article as:
Gasparini, S. & DiFrancesco, D. Pflügers Arch (1997) 435: 99. doi:10.1007/s004240050488


 The effects of ZD 7288, a ”bradycardic” agent, in young rat hippocampal slices in vitro were studied. ZD 7288 (1–1000 μM) reduced the hyperpolarization-activated current (Ih) in CA1 pyramidal neurons by a voltage-independent blocking mechanism. Under current-clamp conditions, the bradycardic agent (10 μM) caused membrane hyperpolarization (by 5.9 ± 0.5 mV) and a reduction of membrane conductance (by 17.9 ± 4.1%). These data are consistent with the block of an inward current which is active at rest. The drug-induced hyperpolarization depressed the cell’s excitability by increasing the threshold current necessary to induce firing. When the drug-induced hyperpolarization was compensated for by injection of a tonic depolarizing current, ZD 7288 caused a reduction of the inhibitory post-synaptic potential (IPSP) in EPSP-IPSP sequences. Since Cs+, another known blocker of Ih, is able to reverse long-term depression (LTD) of the CA3-CA1 synapse in hippocampal slices, we tested the effect of ZD 7288 on synaptic transmission. We found that ZD 7288 did not significantly modify LTD, suggesting that Cs+-induced inhibition of LTD maintenance is not directly related to block of Ih.

Key words Hyperpolarization-activated current (Ih) Hippocampal slices CA1 pyramidal neurons Bradycardic agents ZD 7288 

Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • S. Gasparini
    • 1
  • D. DiFrancesco
    • 1
  1. 1.Università di Milano, Dipartimento di Fisiologia e Biochimica Generali, Elettrofisiologia, via Celoria 26, I-20133 Milan, ItalyIT

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