Potent inhibition by trivalent cations of ATP-gated channels.
The effects of La3+ and other trivalent cations on ATP-gated channels (P2X purinoceptor/channels) were investigated using rat pheochromocytoma PC12 cells and Xenopus oocytes expressing these channels. La3+, Gd3+, Ce3+ and Nd3+ (30-300 microM) inhibited an inward current activated by 30 microM ATP in PC12 cells. The concentration-response curve for the ATP-activated current was shifted by La3+ or Gd3+ toward a higher concentration range, and the slope of the curve became steeper, suggesting the inhibition is non-competitive. La3+ or Gd3+ did not affect the current component that was slowly activated upon hyperpolarization, and selectively inhibited the remaining 'voltage-independent' component. La3+ and Gd3+ also inhibited currents mediated through P2X1 and P2X2 purinoceptors expressed in Xenopus oocytes. The results suggest that La3+ and other trivalent cations inhibit P2X purinoceptors at low concentrations. The inhibition may at least partly be attributed to an allosteric inhibition.
Nakazawa
K
K
Division of Pharmacology, National Institute of Health Sciences, Setagaya, Tokyo, Japan.
Liu
M
M
Inoue
K
K
Ohno
Y
Y
D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002412:Cations / Q000494:pharmacology; D005260:Female; D005682:Gadolinium / Q000494:pharmacology; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D007811:Lanthanum / Q000494:pharmacology; D008564:Membrane Potentials; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D016716:PC12 Cells; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000378:metabolism; D014981:Xenopus
D002412:Cations; D007473:Ion Channels; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D007811:Lanthanum; D000255:Adenosine Triphosphate; D005682:Gadolinium