Ca(2+) influx triggered by depletion of sarcoplasmic reticulum (SR) Ca(2+) stores [mediated via store-operated Ca(2+) channels (SOCC)] was characterized in enzymatically dissociated porcine airway smooth muscle (ASM) cells. When SR Ca(2+) was depleted by either 5 microM cyclopiazonic acid or 5 mM caffeine in the absence of extracellular Ca(2+), subsequent introduction of extracellular Ca(2+) further elevated [Ca(2+)](i). SOCC was insensitive to 1 microM nifedipine- or KCl-induced changes in membrane potential. However, preexposure of cells to 100 nM-1 mM La(3+) or Ni(2+) inhibited SOCC. Exposure to ACh increased Ca(2+) influx both in the presence and absence of a depleted SR. Inhibition of inositol 1,4,5-trisphosphate (IP)-induced SR Ca(2+) release by 20 microM xestospongin D inhibited SOCC, whereas ACh-induced IP(3) production by 5 microM U-73122 had no effect. Inhibition of Ca(2+) release through ryanodine receptors (RyR) by 100 microM ryanodine also prevented Ca(2+) influx via SOCC. Qualitatively similar characteristics of SOCC-mediated Ca(2+) influx were observed with cyclopiazonic acid- vs. caffeine-induced SR Ca(2+) depletion. These data demonstrate that a Ni(2+)/La(3+)-sensitive Ca(2+) influx via SOCC in porcine ASM cells involves SR Ca(2+) release through both IP(3) and RyR channels. Additional regulation of Ca(2+) influx by agonist may be related to a receptor-operated, noncapacitative mechanism.

Neurotrophins [e.g., brain-derived neurotrophic factor (BDNF), neurotrophin 4 (NT4)], known to affect neuronal structure and function, are expressed in nonneuronal tissues including the airway. However, their function is unclear. We examined the effect of acute vs. prolonged neurotrophin exposure on regulation of airway smooth muscle (ASM) intracellular Ca(2+) concentration ([Ca(2+)](i)): sarcoplasmic reticulum (SR) Ca(2+) release and Ca(2+) influx (specifically store-operated Ca(2+) entry, SOCE). Human ASM cells were incubated for 30 min in medium (control) or 1 or 10 nM BDNF, NT3, or NT4 (acute exposure) or overnight in 1 nM BDNF, NT3, or NT4 (prolonged exposure) and imaged after loading with the Ca(2+) indicator fura-2 AM. [Ca(2+)](i) responses to ACh, histamine, bradykinin, and caffeine and SOCE following SR Ca(2+) depletion were compared across cell groups. Force measurements were performed in human bronchial strips exposed to neurotrophins. Basal [Ca(2+)](i), peak responses to all agonists, SOCE, and force responses to ACh and histamine were all significantly enhanced by both acute and prolonged BDNF exposure (smaller effect of NT4) but decreased by NT3. Inhibition of the BDNF/NT4 receptor trkB by K252a prevented enhancement of [Ca(2+)](i) responses. ASM cells showed positive immunostaining for BDNF, NT3, NT4, trkB, and trkC (NT3 receptor). These novel data demonstrate that neurotrophins influence ASM [Ca(2+)](i) and force regulation and suggest a potential role for neurotrophins in airway diseases.

Study Design. Retrospective analysis of prospectively collected data. Objective. To report the follow-up curve behaviors in different Sanders staging groups. Summary of Background Data. Vertebral body tethering (VBT) is a growth modulation technique that allows gradual spontaneous follow-up curve correction as the patient grows. There is a lack of scientific evidence regarding appropriate patient selection and timing of implantation. Methods. Patients were grouped into five as: Sanders 1, 2, 3, 4–5, and 6–7. Data were collected preoperatively, at the day before discharge, and at each follow-up. Outcome measures were pulmonary and mechanical complications, readmission, and reoperation rates. Demographic, perioperative, clinical, radiographic, and complication data were compared using Fisher–Freeman–Halton exact tests for categorical variables and Kruskal-Wallis tests for the continuous variables. Results. Thirty-one (29 F, 2 M) consecutive patients with a minimum of 12 months of follow-up were included. The mean age at surgery was 12.1 (10–14). The mean follow-up was 27.1 (12–62) months. The mean preoperative main thoracic curve magnitude was 47° ± 7.6°. For all curves, preoperative and first erect curve magnitudes, bending flexibility, and operative correction percentages were similar between groups (for all comparisons, P > 0.05). The median height gained during follow-up was different between groups (P < 0.001), which was reflected into median curve correction during follow-up. Total curve correction percentage was different between groups (P = 0.009). Four (12.9%) patients had pulmonary and six (19.4%) had mechanical complications. One (3.2%) patient required readmission and two (6.5%) required reoperation. Occurrence of pulmonary complications was similar in Sanders groups (P = 0.804), while mechanical complications and overcorrection was significantly higher in Sanders 2 patients (P = 0.002 and P = 0.018). Conclusion. Follow-up curve behavior after VBT is different in patients having different Sanders stages. Sanders 2 patients experienced more overcorrection, thus timing and/or correction should be adjusted, since Sanders 3, 4, and 5 patients displayed a lesser risk of mechanical complications. Level of Evidence: 3.

Volatile anesthetics inhibit a Ni/La-sensitive store-operated Ca(2+) influx mechanism in porcine ASM cells, which likely helps maintain anesthetic-induced bronchodilation.