Functional consequence of BDNF-induced changes in Ca²⁺ regulatory protein expression.

<p>Small interference RNA (siRNA) inhibition of CD38, Orai1 or STIM1 expression substantially reduced peak [Ca²⁺]_i responses to histamine not only in cells exposed to vehicle only (i.e. no BDNF), but also in those exposed for 24 h to BDNF (A). Transfection agent (Lipofectamine) or nonsense siRNA had no effect on [Ca²⁺]_i responses in either group (not shown). In contrast, siRNA inhibition of TRPC3 had substantially less effect on BDNF enhancement of peak [Ca²⁺]_I, suggesting that the other mechanisms were functionally linked to BDNF effects, and consistent with no change in TRPC3 expression. Similarly, in ASM cells exposed to BDNF for 24 h, inhibition of RyR channels (high concentration ryanodine) or IP₃ channels (Xestospongin C, XeC) or of SERCA (with cyclopiazonic acid; CPA) significantly blunted BDNF enhancement of peak [Ca²⁺]_i responses to histamine (B). *Significant difference from control; #Significant effect of inhibitor. Values are means ± SE (n = 4 patients).