Potassium currents operated by thyrotrophin‐releasing hormone in dissociated CA1 pyramidal neurones of rat hippocampus.

Satoru Ebihara, N. Akaike

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    1. Membrane currents activated by thyrotrophin‐releasing hormone (TRH) were investigated in the dissociated rat hippocampal CA1 pyramidal neurone using the nystatin perforated patch recording configuration. 2. Under current‐clamp condition, TRH caused a transient hyperpolarization accompanied by a decrease of firing activity and a successive long‐lasting depolarization. The latter induced a blockade of firing. 3. When neurones were held at a holding potential (VH) of ‐40 mV under voltage clamp, TRH elicited a transient outward current with an increase in the membrane conductance, which was followed by a sustained inward current with a decrease in membrane conductance. The inactive TRH metabolite, TRH free acid, did not induce any currents. 4. The reversal potential of TRH‐induced outward current (ETRH) was close to the K+ equilibrium potential (EK). The change in ETRH for a 10‐fold change in extracellular K+ concentration was 56.4 mV, indicating that the membrane behaves like a K+ electrode in the presence of TRH. On the other hand, the TRH‐induced inward current was due to suppression of a slow inward current relaxation during hyperpolarizing voltage commands to ‐50 mV from a VH of ‐40 mV, indicating the suppression of the voltage‐ and time‐dependent component of the K+ current (M‐current). 5. The TRH‐induced outward current (ITRH) increased in a concentration‐dependent manner over the concentration range 10(‐8)‐10(‐6) M. The half‐maximum concentration was 7.4 x 10(‐8) M and the Hill coefficient was 1.5. 6. The TRH‐induced outward current (ITRH) was antagonized by K+ channel blockers such as tetraethylammonium (TEA), 4‐aminopyridine (4‐AP) and Ba2+ in a concentration‐dependent manner. ITRH was insensitive to both apamin and iberiotoxin. 7. The first application of TRH to neurones perfused with Ca(2+)‐free external solution containing 2 mM EGTA could induce ITRH but the TRH response diminished dramatically with successive applications. Intracellular perfusion with a Ca2+ chelator, 1,2‐bis(O‐aminophenoxy)ethane‐N,N,N',N'‐tetraacetic acid (BAPTA), also diminished the TRH response. 8. The depletion of Ca2+ from the intracellular Ca2+ store by thapsigargin blocked the TRH response without affecting the caffeine response. Pretreatment with Li+ significantly enhanced ITRH, suggesting that ITRH is involved in the elevation of intracellular free Ca2+ released from the inositol 1,4,5‐trisphosphate (IP3)‐sensitive Ca2+ store site but not from the caffeine‐sensitive one. 9. Staurosporine, a protein kinase C (PKC) inhibitor, suppressed ITRH in a concentration‐dependent manner (the half‐maximum inhibitory concentration (IC50), was 2.45 x 10(‐8) M).(ABSTRACT TRUNCATED AT 400 WORDS)

    元の言語English
    ページ(範囲)689-710
    ページ数22
    ジャーナルThe Journal of Physiology
    472
    発行部数1
    DOI
    出版物ステータスPublished - 1993 12 1

    ASJC Scopus subject areas

    • Physiology

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