Noradrenaline modulates the membrane potential in medial prefrontal cortex pyramidal neurons via β1-adrenergic receptors and HCN channels

• Autorzy: Grzelka K. , Gawlak M. , Szulczyk P.
• Języki publikacji: EN

Abstrakty

EN

The noradrenergic system is essential in medial pre‑ frontal cortex (mPFC) physiology: noradrenaline (NA) acting via adrenergic receptors (α1, α2 and β) plays a sig‑ nificant role in the regulation of cognitive brain functions and affective processes. Impaired modulation of the mPFC by NA has been implicated in many neuropsychiatric dis‑ eases, e.g. posttraumatic stress disorder, attention deficit hyperactivity disorder, and depression. While the pres‑ ence of all adrenergic receptor subtypes has been report‑ ed in the mPFC, little is known regarding the mechanisms by which NA modulates mPFC neurons. The aim of this study was to investigate which adrenergic receptor sub‑ type controls the resting membrane potential and hold‑ ing currents in mPFC neurons. Secondly, we wanted to de‑ fine the cellular effector(s) and signaling pathway(s) in‑ volved in the action of NA. To answer these questions, we recorded the membrane potential and holding current us‑ ing patch‑clamp techniques. Gramicidin perforated‑patch and classical whole‑cell recordings were obtained from layer V mPFC pyramidal neurons in slices isolated from young rats. Distribution of the adrenergic receptor sub‑ types in mPFC was visualized with fluorescent immuno‑ histochemistry. NA evoked depolarization and inward cur‑ rent in the tested cells. Stimulation of α1‑ and α2‑receptors failed to evoke similar effects. Meanwhile, the nonselective β‑receptor agonist, as well as the selective β1‑receptor ag‑ onist, mimicked the effect of NA on holding current. The NA‑dependent inward current was considerably reduced by the selective β1‑receptor antagonist. The effect of NA was also attenuated, though to a smaller degree, by the se‑ lective β3‑receptor antagonist. At the same time, applica‑ tion of two different selective β3‑agonists evoked inward currentsin the tested neurons. Expression of β1‑ and β3‑re‑ ceptors in mPFC was confirmed with confocal microscopy. The β1‑related inward current was greatly decreased in the presence of Cs+ ions and ZD7288, a selective blocker of HCN (hyperpolarization‑activated cyclic nucleotide–gated) channels. It was not affected by selective blockers of dif‑ ferent signaling pathways known to be responsible for me‑ diating the effects from G‑protein‑coupled receptors (e.g. adenylyl cyclase‑PKA and phospholipase C‑PKC). However, it was significantly diminished by blockers of the βγ sub‑ unit‑dependent transduction system. We conclude that NA modulates the membrane potential and holding current of mPFC pyramidal neurons preferentially via β1‑receptors. The effects occur due to HCN channel activation and are probably mediated in a membrane delimited fashion by a βγ subunit released from the G‑protein. Stimulation of β3‑receptors may be partially responsible for the NA‑relat‑ ed effects. Supported by National Science Centre, Poland, grant 2014/15/N/NZ4/04760 and FW5/PM2/16.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2018
• Tom: 78
• Numer: Suppl.1
• Opis fizyczny: p.9-10

Twórcy

autor

Grzelka K.

• Department of Physiology and Pathophysiology, Medical University of Warsaw, Warsaw, Poland

autor

Gawlak M.

• Department of Physiology and Pathophysiology, Medical University of Warsaw, Warsaw, Poland

autor

Szulczyk P.

• Department of Physiology and Pathophysiology, Medical University of Warsaw, Warsaw, Poland