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Depression of high‐threshold calcium currents by activation of human D 2 (short) dopamine receptors expressed in differentiated NG108‐15 cells
Author(s) -
Seabrook G.R.,
McAllister G.,
Knowles M.R.,
Myers J.,
Sinclair H.,
Patel S.,
Freedman S.B.,
Kemp J.A.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb14852.x
Subject(s) - nisoldipine , voltage dependent calcium channel , endocrinology , medicine , calcium , biophysics , patch clamp , chemistry , dihydropyridine , quinpirole , receptor , nifedipine , dopamine , dopamine receptor d2 , biology
1 This study examined the regulation of calcium currents in differentiated NG108‐15 cells that had been stably transfected with cDNA encoding the short isoform of the human D 2 dopamine receptor. Whole cell calcium currents were recorded by nystatin‐perforated patch clamp recording. 2 Transient low‐threshold calcium currents elicited by depolarizations from − 100 mV to − 20 mV were reversibly depressed by NiCl 2 (84 ± 8% at 30 μ m ; n = 3) and by ω‐agatoxin IVA (15 ± 5%; 100 n m , n = 7). These currents were unaffected by hD 2 receptor activation. 3 High‐threshold calcium currents elicited by depolarizations from − 80 mV to 0 mV were partly blocked by ω‐conotoxin GVIA (67 ± 6% at 100 n m , n = 4) and by the subsequent addition of the dihydropyridine, nisoldipine (94 ± 3% at 1 μ m ). Consistent with the presence of at least two distinct types of high‐threshold calcium channels, nisoldipine alone (38 ± 15% at 1 μ m , n = 6) did not preclude the inhibition caused by ω‐conotoxin GVIA (69 ± 13% at 100 n m , n = 4). The residual current was completely blocked by 100 μ m CdCl 2 (98.8 ± 0.4%, n = 7). 4 In hD 2 ‐transfected cells, but not untransfected cells, high‐threshold currents were depressed by quinpirole (30 ± 4% at 100 n m ; n = 15) with a pEC 50 of 8.61 ± 0.22 ( n = 5), as well as by (−)‐noradrenaline (28 ± 5% at 1 μ m , n = 9). Responses to both agonists were selectively antagonized by S‐(−)sulpiride (100 n m ) but not by the α‐adrenoceptor antagonist, phentolamine (10 μ m ). The depression caused by (−)‐noradrenaline was positively correlated with that of quinpirole for each cell ( r 2 = 0.91, slope = 0.99). 5 hD 2 ‐receptor‐mediated inhibition of high‐threshold calcium currents was abolished by pretreatment of cells with ω‐conotoxin GVIA (100 n m ; n = 4). However, a component of the high‐threshold current was reversibly depressed by ω‐conotoxin GVIA (67% to 45% depression after 10 min wash). This current was also depressed by hD 2 receptor activation (59 ± 9% depression in 100 n m quinpirole, n = 3), and was completely blocked by nisoldipine (95 ± 2% at 1 μ m ). 6 These data demonstrate that activation of hD 2 (short) dopamine receptors can regulate both ω‐conotoxin GVIA, and dihydropyridine‐sensitive high‐threshold calcium currents in neuroblastoma cells. Morever, the ability of human D 2 dopamine receptors to regulate more than one type of calcium current supports the notion that these receptors have a diverse functional role in the central nervous system.