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Basal tearing is crucial to maintaining ocular surface wetness. Corneal cold thermoreceptors sense small oscillations in ambient temperature and change their discharge accordingly. Deletion of the cold-transducing ion channel Transient receptor potential cation channel subfamily M member 8 (TRPM8) in mice abrogates cold responsiveness and reduces basal(More)
Molecular determinants of threshold differences among cold thermoreceptors are unknown. Here we show that such differences correlate with the relative expression of I(KD), a current dependent on Shaker-like Kv1 channels that acts as an excitability brake, and I(TRPM8), a cold-activated excitatory current. Neurons responding to small temperature changes have(More)
Cold-sensitive nerve terminals (CSNTs) encode steady temperatures with regular, rhythmic temperature-dependent firing patterns that range from irregular tonic firing to regular bursting (static response). During abrupt temperature changes, CSNTs show a dynamic response, transiently increasing their firing frequency as temperature decreases and silencing(More)
Amyotrophic lateral sclerosis (ALS) is a devastating paralytic disorder caused by dysfunction and degeneration of motoneurons starting in adulthood. Recent studies using cell or animal models document that astrocytes expressing disease-causing mutations of human superoxide dismutase 1 (hSOD1) contribute to the pathogenesis of ALS by releasing a neurotoxic(More)
Transient receptor potential melastatin 8 (TRPM8) is the best molecular candidate for innocuous cold detection by peripheral thermoreceptor terminals. To dissect out the contribution of this cold- and menthol-gated, nonselective cation channel to cold transduction, we identified BCTC [N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)piperazine-1-carboxamide](More)
TRPM8, a member of the melastatin subfamily of transient receptor potential (TRP) cation channels, is activated by voltage, low temperatures and cooling compounds. These properties and its restricted expression to small sensory neurons have made it the ion channel with the most advocated role in cold transduction. Recent work suggests that activation of(More)
TRPM8 is a member of the transient receptor potential ion channel superfamily, which is expressed in sensory neurons and is activated by cold and cooling compounds, such as menthol. Activation of TRPM8 by agonists takes place through shifts in its voltage activation curve, allowing channel opening at physiological membrane potentials. Here, we studied the(More)
Hyperpolarization-activated currents (I(h)) are mediated by the expression of combinations of hyperpolarization-activated, cyclic nucleotide-gated (HCN) channel subunits (HCN1-4). These cation currents are key regulators of cellular excitability in the heart and many neurons in the nervous system. Subunit composition determines the gating properties and(More)
In toad olfactory neurons, a putrid odorant mixture inducing inhibitory responses increases Ca2+-activated K+ conductance, developing a hyperpolarizing receptor potential. Removal of extracellular Ca2+ or exposure to nifedipine reversibly reduced the inhibitory response, suggesting that odorants induce a Ca2+ influx. We show evidence for an odorant-induced(More)