Pannexin-1 Modulates Inhibitory Transmission and Hippocampal Synaptic Plasticity

Abstract

Pannexin-1 (Panx1) hemichannel is a non-selective transmembrane channel that may play important roles in intercellular signaling by allowing the permeation of ions and metabolites, such as ATP. Although recent evidence shows that the Panx1 hemichannel is involved in controlling excitatory synaptic transmission, the role of Panx1 in inhibitory transmission remains unknown. Here, we studied the contribution of Panx1 to the GABAergic synaptic efficacy onto CA1 pyramidal neurons (PyNs) by using patch–clamp recordings and pharmacological approaches in wild-type and Panx1 knock-out (Panx1-KO) mice. We reported that blockage of the Panx1 hemichannel with the mimetic peptide 10Panx1 increases the synaptic level of endocannabinoids (eCB) and the activation of cannabinoid receptors type 1 (CB1Rs), which results in a decrease in hippocampal GABAergic efficacy, shifting excitation/inhibition (E/I) balance toward excitation and facilitating the induction of long-term potentiation. Our finding provides important insight unveiling that Panx1 can strongly influence the overall neuronal excitability and play a key role in shaping synaptic changes affecting the amplitude and direction of plasticity, as well as learning and memory processes.

Panx1 Ablation Aggravates Oxidative Stress and Cell Death by Altering AMPK/mTOR signaling Pathways and the Composition of Synapses in the Zebrafish

“…Furthermore, loss of Panx1 caused altered learning and memory in mice such as diminished cognitive functions including altered spatial reference memory, or spatial reversal learning 42,63,69,41 . Collectively, these studies demonstrate a regulatory role for Panx1 in modulating balance toward excitation and facilitating the induction of long-term potentiation 73 . Further, we have reported a pathway that connects NMDA receptor signaling to the opening of electrical synapse protein Cx36 via Panx1 and CaMK2a, suggesting active participation of Panx1 in modulating both chemical and electrical synapse function by using a shared molecular machinery 74 .…”

“…Panx1 coupling to NMDA receptor functions via Src 28 , STIM1/2 26 or actin, and Rho GTPases, appear to be relevant forsynapse stability 64 . Panx1 channel blockage with the mimetic peptide 10 Panx1 increases the synaptic level of endocannabinoids (eCB) and the activation of cannabinoid receptors type 1 (CB1Rs), decreasing hippocampal GABAergic efficacy and shifting excitation/inhibition (E/I) balance toward excitation and facilitating the induction of long-term potentiation 73 . Further, we have reported a pathway that connects NMDA receptor signaling to the opening of electrical synapse protein Cx36 via Panx1 and CaMK2a, suggesting active participation of Panx1 in modulating both chemical and electrical synapse function by using a shared molecular machinery 74 .…”