LDCVs are synthesized and NPY release remains reduced in shRNA-syt I knockdown cells when syt IV is upregulated by forskolin treatment. (A) Large dense core vesicles are apparent in both control and fsk-treated cells. Electron micrographs reveal that in the control PC12 cells (top panels) and in the syt I knockdown cells (lower panels), both untreated (left side) and fsk-treated (right side) have large dense core vesicles (example shown in each panel by arrowhead). Scale bar = 500 nm. (B) The average stimulated NPY release from 9-12 independent experiments is plotted. Untreated and forskolin-treated control cells, and two independent syt I knockdown cell lines (shRNA-syt Ia and shRNA-syt Ic) were stimulated for 15 min with high K+ to evoke NPY release (**p < 0.01).