Atypical changes in DRG neuron excitability and complex pain phenotype associated with a Na_v1.7 mutation that massively hyperpolarizes activation.

ABSTRACT: Sodium channel Na_v1.7 plays a central role in pain-signaling: gain-of-function Na_v1.7 mutations usually cause severe pain and loss-of-function mutations produce insensitivity to pain. The Na_v1.7 I234T gain-of-function mutation, however, is linked to a dual clinical presentation of episodic pain, together with absence of pain following fractures, and corneal anesthesia. How a Na_v1.7 mutation that produces gain-of-function at the channel level causes clinical loss-of-function has remained enigmatic. We show by current-clamp that expression of I234T in dorsal root ganglion (DRG) neurons produces a range of membrane depolarizations including a massive shift to >-40 mV that reduces excitability in a small number of neurons. Dynamic-clamp permitted us

SUBMITTER: Huang J 

PROVIDER: S-EPMC5788866 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature