Ionic involvement and kinase activity on the mechanism of nongenomic action of thyroid hormones on 45Ca2+ uptake in cerebral cortex from young rats.

Thyroid hormones (TH) play important roles in brain development. Although most of the nongenomic actions of TH are known to be calcium-dependent, the effects of 3,5,3'-triiodo-L-thyronine (T(3)) or thyroxine (T(4)) on calcium influx in cerebral cortex of rats are not clear. In this study we investigate some mechanisms involved in the effect of T(3) and T(4) on Ca(2+) uptake in slices of cerebral cortex from 10-day-old male rats. Results indicated 10(-6)M T(3) or 10(-7)M T(4) was able to increase (45)Ca(2+) uptake after 30s of hormone exposure. The involvement of L- and T-type voltage-dependent Ca(2+) channels (VDCC) on the effect of TH on (45)Ca(2+) uptake was evidenced by using nifedipine and flunarizine, L- and T-type channel blockers, respectively. Otherwise, chloride currents were not involved in the hormone actions, as demonstrated by using 9-anthracene carboxylic acid, a Cl(-)-channel blocker. In addition, results demonstrated a PKC-dependent mechanism for both T(3) and T(4), as evidenced by stearoylcarnitine chloride, a specific PKC inhibitor. Furthermore, we verified that the T(3) action was also mediated by PKA activity, as demonstrated coincubating T(3) and KT 5720 (PKA inhibitor), and reinforced by using theophylline, a phosphodiesterase inhibitor. In contrast, concerning the effect of T(4), results suggest a partial involvement of PKA activity, and demonstrated that high cAMP levels were not able to support the effect of T(4), suggesting the participation of G inhibitory protein-coupled receptor in the action of this hormone on (45)Ca(2+) uptake. In conclusion, our results evidence a nongenomic action of TH promoting Ca(2+) influx by ionic channels involving mechanisms dependent on kinase activities. It is possible that the modulation of Ca(2+) channels by kinase activities represent an important membrane action of TH signaling mechanism in the central nervous system during development.