Blockade by NNC 55-0396, mibefradil, and nickel of calcium and exocytotic signals in chromaffin cells: Implications for the regulation of hypoxia-induced secretion at early life

Abstract

Adrenal chromaffin cells (CCs) express high voltage activated calcium channels (high-VACCs) of the L, N and PQ subtypes; in addition, T-Lype low-VACCs are also expressed during embryo and neonatal life. Effects of the more frequently used T channel blockers NNC 55-0396 (NNC), mibefradil, and Ni2 + on the whole -cell Ba2 vertical bar current (lBa), the K vertical bar -elicited ICa2 vertical bar]c transients and caLecholamine secretion have been studied in adult bovine CCs (BCCs) and rat embryo CCs (RECCs). NNC, rnibefradil, and Ni2 + blocked BCC lBa with 1050 of 1.8, 4.9 and 70 mu M, while IC50 to block lBa in RECCs were 2.1, 44 and 41 Pronounced blockade of K I -elicited ICa2 I]c transients and secretion was also elicited by the three agents. However, the hypoxia-induced secretion (HIS) of caLecholamine iii RECCs was blocked substantially (75%) with thresholds concentrations of NCC (IC20 to block IBa); this was not the case for mibefradil and Ni2 + that required higher concentrations to block the HIS response. Thus, out of the three compounds, NNC seemed to be an adequate pharmacological tool to discern the contribution of T channels to the HIS response, without a contamination with high-VACC blockade. (C) 2015 Published by Elsevier B.V.