Bronchial Muscle Peristaltic Activity in the Fetal Rat

Abstract

Aside for the potential for tonic contraction, the airway smooth muscle exhibits intermittent phasic rhythmic activity that may contribute to lung growth during fetal life. Therefore, we examined 4th generation rat 18 -22 d gestation fetal, 4 -6 d of age newborn and adult bronchial ring from Sprague Dawley rats to compare differences in smooth muscle function. We hypothesized that phasic contractions were greatest before birth. Bronchial muscle spontaneous rhythmic contractions were greatest in the fetus and absent in the adult. In response to KCl stimulation, the fetal bronchial smooth muscle only developed tonic force that was 3.5 Ϯ 0.6 and lower than measured in the newborn 9.0 Ϯ 0.3 and adult 13.7 Ϯ 1.4mN/mm 2 . The thromboxane A 2 analogue U46619 induced tonic and phasic muscle contractions and the amplitude and frequency of the phasic contractions were greater in the fetus as compared with the adult and increased with gestational age. The U46619-induced rhythmic contractions were abrogated by ryanodine, thapsigargin and reduction of extracellular Na ϩ , suggesting intracellular Ca 2ϩ dependence and involvement of the Na ϩ /Ca 2ϩ exchanger. The inward rectifier K ϩ blocker BaCl 2 induced phasic contractions in unstimulated fetal, but not adult bronchial muscle of the same amplitude and frequency as for the spontaneous and U46619-induced ones. We conclude that the airway smooth muscle phasic activity is greatest in the fetus and tends to disappear post-natally with age suggesting an in utero role during lung development.

Enhanced airway smooth muscle cell thromboxane receptor signaling via activation of JNK MAPK and extracellular calcium influx

“…Consequently, it has been hypothesized that the intracellular calcium concentration is abnormally elevated in asthmatic airway smooth muscle cells (Amrani and Panettieri, 1998;Amrani et al, 2004;Moynihan et al, 2008). The U46619-induced tonic contractions in rat bronchi is dependent on the extracellular calcium concentration, while it was not affected by intracellular calcium pools (Parvez et al, 2006). In the present study, calcium-free media in the presence of Ca 2+ chelator EGTA resulted in complete suppression of the U46619-induced contraction in both fresh and organ cultured bronchial segments.…”

“…To evaluate the role of intracellular Ca 2+ signaling in mediating the enhancement of U46619-induced contraction, the inhibitory effects of calcium-free solution in the presence of the Ca 2+ chelator EGTA (1 mM) (Parvez et al, 2006), the voltage-gated calcium channel (VGCC) blocker nifedipine (10 μM) (Skogvall et al, 2007) and the receptor-operated calcium channel (ROCC) blocker SKF96365 (10 μM) (Merritt et al, 1990) were determined in both fresh and organ cultured segments.…”

Ionic mechanisms and Ca2+ handling in airway smooth muscle

“…[135][136][137][138]. The current authors later showed the importance of this mechanism in SR refilling in bovine ASM [16], as have others in murine ASM [139]. This Ca 2+ -influx pathway appears to be dependent on the availability of extracellular Na + [16].…”

Exploiting mechanical stimuli to rescue growth of the hypoplastic lung

“…From the earliest stages of lung development and throughout subsequent prenatal life the developing lung is itself vigorously mechanically active [74][75][76][77]. Peristaltic waves of airway smooth muscle (ASM) rhythmically propagate throughout the airway tree with resulting propulsion of all important lung liquid (Fig.…”