Thermal sensitivity of voltage-gated Na+ channels and A-type K+ channels contributes to somatosensory neuron excitability at cooling temperatures

摘要

Cooling temperatures may modify action potential firing properties to alter sensory modalities. Here we investigated how cooling temperatures modify action potential firing properties in two groups of rat dorsal root ganglion (DRG) neurons, tetrodotoxin-sensitive (TTXs) Na⁺ channel-expressing neurons and tetrodotoxin-resistant (TTXr) Na⁺ channel-expressing neurons. We found that multiple action potential firing in response to membrane depolarization was suppressed in TTXs neurons but maintained or facilitated in TTXr neurons at cooling temperatures. We showed that cooling temperatures strongly inhibited A-type K⁺ currents (IA) and TTXs Na⁺ channels but had fewer inhibitory effects on TTXr Na⁺ channels and non-inactivating K⁺ currents (IK). We demonstrated that the sensitivity of A-type K⁺ channels and voltage-gated Na⁺ channels to cooling temperatures and their interplay determine somatosensory neuron excitability at cooling temperatures. Our results provide a putative mechanism by which cooling temperatures modify different sensory modalities including pain.