Nasal obstruction and consequent
mouth breathing have been shown to change the acid-base balance, producing
respiratory acidosis. Additionally, there exists a large body of evidence maintaining that
acidosis affects the activity of
ATP-sensitive
potassium (K(
ATP)) channels, which play a crucial role in the function of the central nervous system (CNS), for example, in modulating seizure threshold. Thus, in the study described here, we examined whether
mouth breathing, induced by surgical
ligation of nostrils, could affect the seizure threshold induced by
pentylenetetrazole in male NMRI mice. Using the selective K(
ATP) channel opener (
diazoxide) and blocker (
glibenclamide), we also evaluated the possible role of K(
ATP) channels in this process. Our data revealed that seizure threshold was increased 6 to 72 hours after
nasal obstruction, reaching a peak 48 hours afterward, compared with either control or
sham-operated mice (P<0.01). There was a significant decrease in pH of arterial blood samples and increase in CO(2) partial pressure (PCO(2)) during this time. Systemic injection of
glibenclamide (1 and 2mg/kg, ip, daily) significantly prevented the increase in seizure threshold in 48-hour bilaterally nasally obstructed mice, whereas it had no effect on seizure threshold in
sham-operated mice. Systemic injection of
diazoxide (25mg/kg, ip, daily) had no effect on seizure threshold in all groups, whereas higher doses (50 and 100mg/kg, ip, daily) significantly increased seizure threshold in both 48-hour-obstructed and
sham-operated mice. The decrease in seizure threshold induced by
glibenclamide (2mg/kg, ip, daily) was prevented by
diazoxide (25mg/kg, ip, daily). These results demonstrate for the first time that
mouth breathing, which could result in
respiratory acidosis, increases seizure threshold in mice and K(
ATP) channels may play a role in this effect.