Multiple Calcium Pathways Induce the Expression of SNAP‐25 Protein in Chromaffin Cells

: Incubation of bovine adrenal chromaffin cells in high K+ (38 mM) during 24‐48 h enhanced 2.5 to five times the expression of SNAP‐25 protein and mRNA, respectively. This increase was reduced 86% by furnidipine (an L‐type Ca2+ channel blocker) but was unaffected by either ω‐conotoxin GVIA (an N‐type Ca2+ channel blocker) or ω‐agatoxin IVA (a P/Q‐type Ca2+ channel blocker). Combined blockade of N and P/Q channels with ω‐conotoxin MVIIC did, however, block by 76% the protein expression. The inhibitory effects of furnidipine were partially reversed when the external Ca2+ concentration was raised from 1.6 to 5 mM. These findings, together with the fact that nicotinic receptor activation or Ca2+ release from internal stores also enhanced SNAP‐25 protein expression, suggest that an increment of cytosolic Ca2+ concentration ([Ca2+]i), rather than its source or Ca2+ entry pathway, is the critical signal to induce the protein expression. The greater coupling between L‐type Ca2+ channels and protein expression might be due to two facts: (a) L channels contributed 50% to the global [Ca2+]i rise induced by 38 mM K+ in indo‐1‐loaded chromaffin cells and (b) L channels undergo less inactivation than N or P/Q channels on sustained stimulation of these cells.