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Carlos Belmonte, Andres Parra, Juana Gallar, Cruz Morenilla, Susana del Olmo, M Carmen Acosta, Felix Viana; Tear Secretion Rate in Mice with Genetically-Induced Changes in Corneal Cold Receptor Nerve Activity. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2587.
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Activity in cold receptor nerve endings of the cornea contributes to maintain basal tear secretion rate (Parra et al., Nat Med 2010;doi:10.1038/nm.2264). Background firing frequency in cold neurons is influenced by the expression of HCN (hyperpolarization-activated, cyclic nucleotide-gated) ion channels that determine the magnitude of the inward rectification current (Ih). We explored whether deletion of Ih modifies the background firing frequency of cold nerve fibers in HCN1 null mice (HNC1-/-) and whether this produces changes in tear secretion rate.
Mice eyes were excised and mounted in a recording chamber, superfused with physiological saline at a basal temperature of 33ºC. Electrical activity was recorded from individual corneal cold endings using glass pipettes applied onto the corneal surface. Spontaneous activity at basal temperature and firing responses to cooling of the perfusion solution down to 20°C were explored in HCN1-/- and wild type (WT) animals. Mean frequency of spontaneous activity at basal temperature (ongoing activity), peak frequency value during the cooling pulses and temperature at the peak frequency response were analyzed. Tear secretion was also measured in anesthetized animals using phenol-red threads.
Mean frequency of the ongoing activity at a basal temperature of 34ºC in corneal cold nerve terminals was 3.3 ± 0.7 impulses/s (n = 10) in WT mice and 6.93 ± 1.2 impulses/s (n = 8) in HCN1-/- mice, the difference being significant (p < 0.05). However, mean tearing rate was similar in both groups of animals (2.2 ± 0.5 mm wetted strip, n = 20 in WT mice and 2.1 ± 0.42 mm, n = 18 in HCN1-/-, p = 0.87).
Basal tearing rate was similar in HCN1-/- and WT mice in spite of the higher background firing rate of corneal cold receptor fibers in the HCN1 null mouse. These results suggest that the activity level of cold thermosensitive corneal nerve endings at normal corneal temperatures maintains a maximal rate of basal tear secretion that cannot be further augmented by increases in firing frequency of cold receptors fibers.
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