Role of T-type calcium channels in the sensory gating function of the thalamus

다국어 초록 (Multilingual Abstract)

Low-voltage activated(LVA) T-type Ca^(2+) channels play crucial roles in the control of cellular excitability under diverse physiological and pathological processes. Recently, studies revealed a novel role of T-type Ca^(2+) channel in the pain sensory pathway by showing that this channel facilitates pain signals in peripheral nociceptors and in the spinal cord. T-type channels are also highly expressed in the thalamus through which noxious signals from spinal cords should pass before reaching the cortex. Upon sensory inputs, thalamocortical relay neurons respond in dual firing modes: either in singular action potentials or in a burst of action potentials clustered together as a high frequency discharges. T-type Ca^(2+) channels are known to excite hyperpolarized thalamic neurons to generate bursts of action potentials. There has been much debate on the role of the thalamic burst firing in the sensory processing. Therefore, it is an open question whether thalamic T-type channels would contribute to the nociceptive signal processing as a signal enhancer or a suppressor.
Sensations from viscera, like fullness, easily become painful if the stimulus persists. Mice lacking 1G T-type Ca^(2+) channels show behavioural hyperalgesia to visceral pain. Thalamic infusion of a T-type blocker, mibefradil, induced similar hyperalgesia in wildtype mice. In response to visceral pain, thalamocortical relay neurons evoked a surge of singular action potentials, which then slowly decayed as the burst firing activity mediated by T-type Ca^(2+) channels gradually increased. In 1G-deficient neurons, the induced single-spike response persisted without burst firing. These results indicate that T-type Ca^(2+) channels underlie an antinociceptive mechanism operating in the thalamus and support the idea that thalamic burst firing plays a critical role in sensory-gating in the thalamus.