| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Research Abstract |
When a prolonged, severe hypoxic condition is induced by ischemia or apnea, animals show a specific respiration pattern consisted of rapid and large inspiration with long respiration interval called gasping in order to maintain minimum oxygen supply and carbone dioxide removal. However, molecular mechanisms underlying central regulation of gasping is unclear.
In the present study, we found that mice lacking ATP-sensitive potassium (KATP) channels containing Kir6.2 subunit (KO mice) show minimum number of gasping after decapitation. Indeed, the number of gasps was significantly smaller, total duration of gasping, are shorter, and the onset of gasping is slower than those of wild-type mice. Similar results were also found in mice subjected to severe (〜5%) hypoxia under urethane-anesthesia. Recordings of phrenic nerve activity further revealed that KO mice did not show phrenice activity having waveform typical of normal gasping except for the last few gasps just before cessation of respiration, suggesting that KATP channels are critically involved in the induction of gasping during severe hypoxia. This hypothesis was further confirmed by mice restrained in a tube under unanesthetized conditions. The body movemement during gasping was successfully detected by piezoelectric device put beneath the mice and a CO2 monitor set within the tube.
On the other hand, Kir6.2-containing KATP channels are expressed most abundantly in GABAergic principal neurons in the midbrain nucleus substantia nigra pars reticulata (SNr), and exert important role for detecting severe hypoxic conditions (Yamada et al, J Mol Cell Cardiol, in press). Here we show that these neurons not only sense hypoxia but also mild hypoglycemia. In the present study, however, we found that the KATP channels in the SNr are not importantly involved in the detection of mild hypoglycemia (Yuan et al, Neurosci Lett, 2004).
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