Depression of high‐threshold calcium currents by activation of human D2 (short) dopamine receptors expressed in differentiated NG108‐15 cells
1994
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 D2 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 NiCl2 (84 ± 8% at 30 μm; n = 3) and by ω-agatoxin IVA (15 ± 5%; 100 nm, n = 7). These currents were unaffected by hD2 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 nm, n = 4) and by the subsequent addition of the dihydropyridine, nisoldipine (94 ± 3% at 1 μm). Consistent with the presence of at least two distinct types of high-threshold calcium channels, nisoldipine alone (38 ± 15% at 1 μm, n = 6) did not preclude the inhibition caused by ω-conotoxin GVIA (69 ± 13% at 100 nm, n = 4). The residual current was completely blocked by 100 μm CdCl2 (98.8 ± 0.4%, n = 7).
4
In hD2-transfected cells, but not untransfected cells, high-threshold currents were depressed by quinpirole (30 ± 4% at 100 nm; n = 15) with a pEC50 of 8.61 ± 0.22 (n = 5), as well as by (−)-noradrenaline (28 ± 5% at 1 μm, n = 9). Responses to both agonists were selectively antagonized by S-(−)sulpiride (100 nm) but not by the α-adrenoceptor antagonist, phentolamine (10 μm). The depression caused by (−)-noradrenaline was positively correlated with that of quinpirole for each cell (r2= 0.91, slope = 0.99).
5
hD2-receptor-mediated inhibition of high-threshold calcium currents was abolished by pretreatment of cells with ω-conotoxin GVIA (100 nm; 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 hD2 receptor activation (59 ± 9% depression in 100 nm quinpirole, n = 3), and was completely blocked by nisoldipine (95 ± 2% at 1 μm).
6
These data demonstrate that activation of hD2(short) dopamine receptors can regulate both ω-conotoxin GVIA, and dihydropyridine-sensitive high-threshold calcium currents in neuroblastoma cells. Morever, the ability of human D2 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.
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