TY - JOUR T1 - Receptor-Mediated Effects of Endothelin on the <span class="sc">l</span>-Type Ca<sup>++</sup> Current in Ventricular Cardiomyocytes JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 662 LP - 669 VL - 286 IS - 2 AU - Elizabeth J. Kelso AU - J. Paul Spiers AU - Barbara J. McDermott AU - C. Norman Scholfield AU - Bernard Silke Y1 - 1998/08/01 UR - http://jpet.aspetjournals.org/content/286/2/662.abstract N2 - The purpose of this study was to establish whether specific receptor subtypes are responsible for mediating the effects of endothelin-1 (ET-1) and endothelin-3 (ET-3) on the l-type calcium current (ICa) using a number of receptor-selective antagonists, including PD155080 (ETA), BQ-788, RES-701 and IRL-1038 (ETB) and the ETA/ETBreceptor-non-selective antagonist PD145065. Ventricular cardiomyocytes were isolated from adult New Zealand White rabbits using Langendorff perfusion with collagenase. ICa was recorded using a whole-cell patch-clamp technique. ET-1 decreased, whereas ET-3 increased, ICa at equimolar concentrations of 10 nM. The decrease in ICa produced by ET-1 was completely blocked by PD155080 and PD145065 (1 and 10 μM); however, ICa was increased upon washout of PD155080. Although the decrease in ICa produced by ET-1 was partially blocked by BQ-788 (1 and 10 μM), ET-1 in combination with either RES-701 (1 and 10 μM) or IRL-1038 (1 μM) produced a decrease in ICa similar to that produced by ET-1 alone. The increase in ICa by ET-3 was completely abolished by either BQ-788 or IRL-1038 (1 μM). These data indicate that the decrease in ICa produced by ET-1 in rabbit ventricular cardiomyocytes is mediated by the ETAreceptor subtype, because PD155080 completely inhibited this response. The ETB receptor-selective antagonists RES-701 and IRL-1038 did not alter the decrease in current produced by ET-1, although the response was partially sensitive to BQ-788, which may lack receptor-subtype selectivity in these cells. In contrast, the increase in ICa produced by ET-3 was mediated by the ETBreceptor subtype, because BQ-788 and IRL-1038 abolished this response. The American Society for Pharmacology and Experimental Therapeutics ER -