Effects of inhibitor of serine/threonine protein phosphatases 1 and 2A on voltage-dependent sodium channels in rat trigeminal ganglion neurons / 中国药理学与毒理学杂志

AIMTo investigate the role of serine/threonine protein phosphatases in regulation of cell signal transduction on voltage-dependent sodium channels in rat trigeminal ganglion (TRG) neurons. METHODSWhole-cell patch clamp techniques were used to record the total sodium current (INa-T) and the tetrodotoxin-resistant sodium current (INa-TTX-R) before and after okadaic acid, a potent inhibitor of the serine/threonine protein phosphatases 1 and 2A, perfusion on adult rat TRG neurons. RESULTS1μmol*L-1 okadaic acid inhibited INa-T by (20±13)% (n=9, P<0.05) and INa-TTX-R by (4±3)% (n=6, P<0.05), respectively. The inhibition on INa-T was significantly greater than that on INa-TTX-R (P<0.05). Furthermore, 1μmol*L-1 okadaic acid produced significant 3-4 mV hyperpolarizing shifts in the conductance-voltage curves of INa-T, while it had no effect on that of INa-TTX-R. CONCLUSIONThe serine/threonine protein phosphatases take part in the regulation of total and TTX-R sodium channels on rat TRG neurons. In addition, small-diameter TRG neurons express various voltage-gated sodium channel with different sensitivity to okadaic acid.

Comparison between effects of AMP579 and adenosine on Na+/Ca2+ exchanger in isolated rat ventricular myocytes / 中国药理学与毒理学杂志

AIMTo elucidate possible mechanisms underlying the differences between 1S-[1a,2b,3b,4a(S*)]-4-[7-[[1-(3-chloro-2-thienyl)methylpropyl]propyl-amino]-3H-imidazo[4,5-b]pyridyl-3-yl]-N-ethyl-2,3-dihydroxycyclopentane carboxamide (AMP- 579) and adenosine in pharmacological and clinical effects. METHODSNa+/Ca2+ exchange current was recorded by patch-clamp technique in whole-cell configuration. RESULTSAMP579 significantly enhanced both outward and inward Na+/Ca2+ exchange currents in a concentration dependent manner. Neither infusion of an adenosine A1 receptor antagonist PD116948 30 μmol*L-1 or an adenosine A2 receptor antagonist DMPX 10 μmol*L-1 nor a protein kinase A special blocker KT 5720 0.2 μmol*L-1 or a protein kinase C special blocker GF 109203X 0.4 μmol*L-1 had effect on Na+/Ca2+exchange current increased by AMP579, suggesting that AMP579 possess a direct activating effect on Na+/Ca2+ exchange current. CONCLUSIONAMP579 possibly possesses a direct activating effect on Na+/Ca2+ exchange current.