BDNF in hypoxia enhancement of intracellular Ca²⁺ ([Ca²⁺]_i) responses to agonist in human PASMCs.

<p>(a) Exposure of PASMCs to 1 μM serotonin (5HT; arrow) resulted in a transient [Ca^<b>2+</b>]_<b>i</b> response. Under normoxic conditions, 24h exposure to 100 pM BDNF enhanced the subsequent response to 1 μM 5HT, as reflected by increased amplitude (bar graph). (b) Hypoxia substantially enhanced [Ca^<b>2+</b>]_<b>i</b> responses of PASMCs to 5HT. Under conditions of hypoxia, BDNF did not produce any additional augmentation of these responses. However, neutralization of extracellular BDNF using the chimeric TrkB-Fc (1 μg/ml) protein blunted the effect of hypoxia. Similarly inhibition of HIF1α reduced the effect of hypoxia on the responses to 5HT. Values are means ± SE (n = 7 patients). *Significant difference from normoxia control, #significant effect of inhibitors from hypoxia control (p<0.05).