α2δ-1 gene deletion affects somatosensory neuron function and delays mechanical hypersensitivity in response to peripheral nerve damage - PubMed (original) (raw)

TRPA1, TRPV1, and TRPM8 responses in α2δ-1+/+ and α2δ-1−/− DRG neurons. A, Representative traces showing changes in cytoplasmic Ca2+ activity (fura-2 AM fluorescence ratio: ratio (F340/F380)) in response to the TRPA1 agonist MO (100 μ

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, applied for 20 s), the TRPM8 agonist ME (500 μ

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, 30 s), the TRPV1 agonist CAPS (1 μ

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, 10 s), and 60 m

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K+ (K, 10 s) in α2δ-1+/+ neurons. B, Quantification of percentage of α2δ-1+/+ (black bars) and α2δ-1−/− (white bars) DRG neurons responding to MO (100 μ

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for 20 s, left), CAPS (1 μ

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for 5 or 10 s, middle), and ME (250 or 500 μ

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for 30 s, right). The number of responses to each agonist was normalized to number of responses to 60 m

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K+ per coverslip. Error bars indicate SEM. Statistical analysis was as follows: unpaired Student's t test comparing α2δ-1+/+ and α2δ-1−/− responses: MO response, p = 0.90 (n = 13 α2δ-1+/+ and n = 18 α2δ-1−/− coverslips); CAPS response, p = 0.005 (n = 29 α2δ-1+/+ and n = 36 α2δ-1−/− coverslips); ME response, p = 0.028 (n = 30 α2δ-1+/+ and n = 37 α2δ-1−/− coverslips). In total, n = 982 α2δ-1+/+ and n = 1151 α2δ-1−/− cells were analyzed. C, Peak fura-2 AM fluorescence ratio (peak ratio: (F340/F380)) for MO, CA, CAPS, and ME responses. Error bars indicate SEM. Statistical analysis was as follows: unpaired Student's t test, comparing α2δ-1+/+ and α2δ-1−/− neurons: MO peak response, p < 0.003 (n = 290 α2δ-1+/+, n = 247 α2δ-1−/− neurons); CA peak response, p = 0.0002 (n = 230 α2δ-1+/+, n = 325 α2δ-1−/− neurons); CAPS peak response, p = 0.011 (n = 189 α2δ-1+/+, n = 191 α2δ-1−/− neurons); ME peak response (250 μ

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), p = 0.98 (n = 55 α2δ-1+/+, n = 49 −/− neurons). *p < 0.05. **p < 0.01. ***p < 0.001.