Ca2+ entry through the L-subtype (alpha(1D), Ca(v)1,3) of voltage-dependent calcium channels (VDCCs) seems to selectively regulate the endocytotic response after the application of a single depolarizing pulse to voltage-clamped bovine chromaffin cells. Here we have found that L channel blockade with nifedipine transformed the exocytotic responses elicited by a double-pulse protocol, from depression to facilitation. This apparent paradoxical effect was mimicked by pharmacological interventions that directly block endocytosis namely, dynasore, calmidazolium, GTP-gamma S and GDP-beta S. This reinforces our view that Ca2+ entry through PQ channels (alpha(1A); Ca(v)2.1) regulates fast exocytosis while Ca2+ entry through L channels preferentially controls rapid endocytosis. (C) 2011 Elsevier Inc. All rights reserved.