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Impairment of long‐term facilitation (LTF) of respiratory motor outputs following intermittent hypoxia and response to hypercapnia in HCN2‐deficient mice.
Author(s) -
Dutschmann Mathias,
Ludwig Andreas,
Kleppisch Thomas
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a373-b
Subject(s) - hypercapnia , respiratory system , excitatory postsynaptic potential , hypoxia (environmental) , phrenic nerve , medicine , knockout mouse , brainstem , endocrinology , chemistry , sinoatrial node , neuroscience , anesthesia , biology , receptor , heart rate , oxygen , organic chemistry , blood pressure
HCN2 channels are hyperpolarization‐activated cyclic nucleotide‐gated channels proposed to function as pacemaker channels the sinoatrial node. The role of HCN channels for oscillatory activity underlying respiratory rhythm generation remains controversial, although they are abundantly expressed in the brainstem. We recorded phrenic (PNA) and hypoglossal nerve activity (XIIA) in the perfused brainstem preparation from wild type (WT) and knockout mice (HCN2−/−). HCN2−/− mice (n=7) had no obvious impairment of respiratory rhythm or pattern compared to WT under undisturbed conditions(n=7). Similarly, no significant differences between the two genotypes were detected following hypoxic challenge (n=5). However, the respiratory response of HCN2−/− mice to hypercapnia (12% CO2, n=5) was blunted. WT mice responded to hypercapnia with an increase in both frequency and burst amplitude of PNA and XIIA. The increase in burst amplitudes in particular on XIIA was strongly reduced in HCN2−/− mice. We further examined LTF to assess a role of HCN2 channels for plasticity at the level of respiratory motoneurones. Intermittent hypoxia (5X, 30s hypoxia in 2 min interval, n=5 each group) induced robust LTF of PNA and XIIA in WT mice, but had only marginal effects in HCN2−/− mice. We suggest that HCN2 channels play a role in modulating the excitatory drive to respiratory motoneurones. Funded by the CMPB Göttingen and SFB 391