Source of voltage-dependency in hydrocortisone block of nicotinic acetylcholine receptor

• Autorzy: Dworakowska B. , Nurowska E. , Dolowy K.
• Języki publikacji: EN

Abstrakty

EN

Corticosteroids have been shown to exert direct inhib‑ itory action on the muscle‑type nicotinic acetylcholine re‑ ceptor (AChR) and therefore can promote pharmacological muscle denervation. The mechanism of hydrocortisone (HC) blockade of AChR has not been fully established. It is uncommon for an electrically neutral molecule, e.g. HC, to induce voltage‑dependent changes in AChR kinetics. Our experiments aimed to determine the source of voltage‑de‑ pendency in HC action. Wild‑type (WT) and αD200Q recep‑ tors were transiently expressed in HEK293 cells. Record‑ ings were performed in either the presence or absence of HC. We showed that the D‑to‑Q substitution is capable of suppressing voltage dependency in the HC‑induced block. We conclude that the distance between αD200 and the ago‑ nist binding site depends on the membrane potential. The voltage‑dependent changes of the αD200 position have not been determined yet. To our knowledge, the ability to in‑ duce voltage‑dependency in blocker action has not been shown previously for an amino acid located outside the transmembrane portion of the receptor. Possible mech‑ anisms of HC block (allosteric and knocking) in WT and αD200Q receptors are proposed.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2018
• Tom: 78
• Numer: Suppl.1
• Opis fizyczny: p.9

Twórcy

autor

Dworakowska B.

• Laboratory of Physiology and Pathology, Centre for Preclinical Research and Technology, Medical University of Warsaw, Warsaw, Poland

autor

Nurowska E.

• Laboratory of Physiology and Pathology, Centre for Preclinical Research and Technology, Medical University of Warsaw, Warsaw, Poland

autor

Dolowy K.

• Laboratory of Physiology and Pathology, Centre for Preclinical Research and Technology, Medical University of Warsaw, Warsaw, Poland