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Role of KCNQ channels in response of the pulmonary circulation to hypoxia
Šedivý, Vojtěch ; Herget, Jan (advisor) ; Melenovský, Vojtěch (referee) ; Neckář, Jan (referee)
Reaction of pulmonary vascular bed to hypoxia is different than in systemic vasculature. Acute ventilatory hypoxia constricts pulmonary arteries (HPV), diverts blood to better oxygenated alveoli and optimises arterial pO2. Chronic hypoxia causes pulmonary hypertension (HPH) and exposure to hypoxia at birth (perinatal hypoxia) results in longterm changes of pulmonary vasculature, which makes it more susceptible to develop pulmonary hypertension in adulthood. Reaction of pulmonary artery smooth muscle cells (PASMCs) to hypoxia involves membrane depolarization by inhibition of voltage gated potassium channels (Kv). Among them KCNQ (Kv7) channels have biophysical properties (low voltage threshold for activation and lack of inactivation during sustained depolarization) which suggest them to play a key role in hypoxic response. Specific KCNQ channel inhibitor linopirdine primes HPV in saline perfused lungs, but in not primed lungs does not cause vasoconstriction, it behaves in the same way as acute ventilatory hypoxia. Moreover, in primed lungs linopirdin potentiates HPV and prevents non- specific Kv inhibitor 4-aminopyridine to potentiate HPV. It seems, that KCNQ channel inhibition has a key role in HPV. In rats exposed to hypoxia for 3-5 days (normobaric chamber, FiO2 0,1) we examined relationship of...
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