BAY-K-8644 REVEALS 2 COMPONENTS OF L-TYPE CA2-CELLS( CHANNEL CURRENT IN CLONAL RAT PITUITARY)

Whole-cell L-type Ca2+ channel current was recorded in GH(3) clonal ra t pituitary cells using Ba2+ as a charge carrier. In the presence of t he dihydropyridine agonist Bay K 8644, deactivation was best described by two exponential components with time constants of similar to 2 and similar to 8 ms when recorded at -40 mV. The slow component activated at more negative potentials than the fast component: Half-maximal act ivation for the slow and fast components occurred at similar to-15 and similar to 1 mV, respectively. The fast component was more sensitive to enhancement by racemic Bay K 8644 than the slow component: ED(50fas t) = similar to 21 nM, ED(50slow) = similar to 74 nM. Thyrotropin-rele asing hormone (TRH; 1 mu M) inhibited the slow component by similar to 46%, whereas the fast component was inhibited by similar to 22%. TRH inhibition of total L-current showed some voltage dependence, but each Bay K 8644-revealed component of L-current was inhibited in a voltage -independent manner. Therefore, the apparent voltage dependence of TRH action is derived from complexities in channel gating rather than fro m relief of inhibition at high voltages. In summary, Bay K 8644-enhanc ed L-currents in GH(3) cells consist of two components with different sensitivities to voltage, racemic Bay K 8644, and the neuropeptide TRH .