EXPRESSION OF DOPAMINE D-2 RECEPTOR IN PC-12 CELLS AND REGULATION OF MEMBRANE CONDUCTANCES BY DOPAMINE

PC-12 cells depolarize during hypoxia and release dopamine. The hypoxi a-induced depolarization is due to inhibition of an O-2-sensitive K+ c urrent. The role of dopamine released during hypoxia is uncertain, but it could act as an autocrine to modulate membrane conductance during hypoxia. The current study was undertaken to investigate this possibil ity. Reverse transcription-polymerase chain reaction and sequence anal ysis revealed that the D-2 isoform of the dopamine receptor is express ed in rat PC-12 cells. Exogenously applied dopamine and the D-2 agonis t quinpirole elicited inhibition of a voltage-dependent K+ current (I- K) that was prevented by sulpiride, a D-2 receptor antagonist. Dopamin e and quinpirole applied during hypoxia potentiated the inhibitory eff ect of hypoxia on I-K. We also found that quinpirole caused reversible inhibition of a voltage-dependent Ca2+ current (I-Ca) and attenuation of the increase in intracellular free Ca2+ during hypoxia. Our result s indicate that dopamine released from PC-12 cells during hypoxia acts via a D-2 receptor to ''autoregulate'' I-K and I-Ca.