Acute activation of 5-HT7 receptors affects electrophysiological properties and synaptic processing of rat CA1 pyramidal cells by inhibiting fast-inactivating potassium currents

• Autorzy: Siwiec M. , Sowa J.E. , Tokarski K. , Hess G.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: Experimental evidence points to the 5-HT7 receptor as a potential therapeutic target for affective and neurodevelopmental disorders. The cellular/ ionic mechanisms following the activation of the 5-HT7 receptor signaling pathway have not yet been fully characterized. Our preliminary recordings from hippocampal neurons have shown that 5-HT7 activation, in addition to increasing neural excitability, shortens action potential latency, which suggests involvement of voltage-gated potassium channels in the neural response to 5-HT7 activation. AIM(S): The aim of our study was to directly investigate modulatory effects of 5‑HT7 activation on voltage‑gated potassium channels in rat CA1 pyramidal cells, as well as to examine the functional consequences of such effects on the hippocampal circuitry. METHOD(S): We performed whole-cell voltage clamp recordings from rat CA1 pyramidal cells and tested the effects of 5‑HT7 agonists on A‑type and delayed rectifier potassium currents. To examine the influence of the 5-HT7-mediated channel modulation on synaptic transmission, we stimulated Schaffer collaterals and recorded evoked AMPA currents before and after 5-HT7 activation, as well as before and after blocking Kv4.3/Kv4.4 and/or HCN channel subunits. RESULTS: Activation of 5-HT7 receptors markedly attenuated A-type potassium currents in CA1 pyramidal cells. Furthermore, 5-HT7 activation increased AMPA postsynaptic currents evoked by stimulation of Schaffer collaterals, and this effect was partially dependent on the inhibition of A-type potassium channels. CONCLUSIONS: We found that 5-HT7 receptors can strongly influence neural activity by inhibiting A‑type potassium currents, which affects both neural excitability and response dynamics, as well as CA3 -> CA1 synaptic transmission. FINANCIAL SUPPORT: The study was supported by Ministry of Science and Higher Education (Warsaw, Poland) grant no 2016/21/B/NZ4/03618 and statutory funds from the Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland. M.S. and J.E.S. are beneficiaries of the KNOW PhD scholarship sponsored by the Ministry of Science and Higher Education, Poland.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.104

Twórcy

autor

Siwiec M.

• Institute of Pharmacology Polish Academy of Sciences, Department of Physiology, Cracow, Poland

autor

Sowa J.E.

• Institute of Pharmacology Polish Academy of Sciences, Department of Physiology, Cracow, Poland

autor

Tokarski K.

• Institute of Pharmacology Polish Academy of Sciences, Department of Physiology, Cracow, Poland

autor

Hess G.

• Institute of Pharmacology Polish Academy of Sciences, Department of Physiology, Cracow, Poland
• Institute of Zoology and Biomedical Research, Jagiellonian University, Cracow, Poland