Activation of 5-HT7 receptors affects neuronal excitability in rat CA1 hippocampus by inhibiting fast inactivating potassium channels

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

Abstrakty

EN

INTRODUCTION: Emerging evidence suggests the 5-HT7 receptor as a therapeutic target in stress-related disorders. Precise effects of the 5‑HT7‑mediated regulation of neuronal excitability remain to be elucidated. Preliminary recordings from rat CA1 piramidal neurons showed that 5-HT7 activation shortens the latency of the first spike in response to depolarization. Due to their rapid kinetics and fast recovery from inactivation, A-type potassium channels (KA) are prime candidates for mediating this effect. AIM(S): The aim of our study was to assess whether the changes in neuronal excitability and response dynamics of CA1 pyramidal cells following the activation of 5-HT7 receptors are due to inhibition of A-type K+ channels. METHOD(S): Whole-cell patch-clamp recordings were performed in current-clamp mode. Neurons were held at −65 mV and their excitability was assessed using depolarizing current pulses. To activate 5-HT7 receptors, 5‑CT (250 nM) was applied along with WAY 100635 (2 µM), a 5-HT1A antagonist. Further recordings were performed in the presence of specific blockers of A‑type and H‑type channels. RESULTS: Activation of 5-HT7 receptors increased the excitability of CA1 pyramidal cells as well as decreased the latency to 1st spike, and effect which was prevented by using a specific Kv4.3/Kv4.4 channel blocker. Blockade of HCN channels did not affect the decrease in spike latency. CONCLUSIONS: Our data show that activation of 5-HT7 influences neuronal excitability in CA1 pyramidal cells partly by inhibiting fast-inactivating A-type potassium channels. These results help further explain the physiological role of the 5-HT7 receptor, hopefully leading to better understanding of its role in nervous system physiology and pathology. FINANCIAL SUPPORT: This study was supported by the Ministry of Science and Higher Education (Warsaw, Poland) grant no 2016/21/B/NZ4/03618 and statutory founds from the Department of Physiology, Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland. J.E.S ans M.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.103-104

Twórcy

autor

Sowa J.E.

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

autor

Siwiec M.

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

autor

Tokarski K.

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

autor

Hess G.

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