Session Speaker

Activation of δ-Opioid Receptors Protects Against Anoxic Disruption Of Ionic Homeostasis In The Cortex
Ying Xia
USA

Hypoxic/ischemic disruption of ionic homeostasis, especially Na⁺ influx, Ca2⁺influx and K⁺ leakage, is a critical trigger of neuronal injury/death in the brain. There is, however, no promising strategy against such pathophysiological change in clinical setting. Recently, we have shown that the activation of d-opioid receptor (DOR) is protective from hypoxic/ischemic injury in cortical neurons. This is, at least partially, attributed to the stabilization of Na⁺-Ca2⁺-K⁺ homeostasis across the membrane because DOR activation attenuates Na⁺Ca2⁺ influxes and K⁺ leakage in the cortex exposed to anoxia. In contrast, activation of Mu-opioid receptors does not induce any significant neuroprotection in the same cortical preparations. Furthermore, we observed that DOR activation restricts Na+ influx through voltage-gated Na⁺channels, and DOR expression and/or activation decrease Na⁺ channel function and reduce Na⁺-influx initiated K⁺ leakage in anoxia, suggesting that Na⁺ channels are an important protein targeted by DOR signal. The exploration of the intracellular pathway shows that DOR-mediated neuroprotection relies on a PKC-dependent and PKA independent pathway. These first data may have far-reaching impacts on understanding the intrinsic mechanism of neuronal responses to stress and provide novel insights into better pharmacological solutions of hypoxic/ischemic encephalopathy and other neurological disorders such as epilepsy and pain.

This work was supported by the grants of NIH-HD34852, NIH-AT004422 and AHA-0755993T.