TGF beta 1 regulates the gating properties of intermediate-conductance K-Ca channels in developing parasympathetic neurons

The developmental expression of Ca2+-activated K+ channels (K-Ca) in chick ciliary ganglion (CG) neurons is regulated by a target-derived avian isofor m of TGF beta 1, which evokes a robust increase in the number of functional large-conductance (BK) K-Ca channels but which produces no change in their kinetics. However, CG neurons express multiple K-Ca channel subtypes. Here we show that TGF beta 1 regulates the gating properties of intermediate-co nductance (IK) K-Ca channels in developing CG neurons. IK channels in insid e-out patches excised from control E9 CG neurons became active on, exposure to 1-5 mu M free Ca2+ but then remained active on return to Ca2+-free sali nes. In contrast, IK channels in TGF beta 1-treated cells became active on exposure to 1-5 mu M Ca2+, but became quiescent immediately on return to Ca 2+-free salines. In contrast to its effects on BK channels, TGF beta 1 had no effect on the mean number of IK channels detected in excised patches. IK channels were not activated in cell-attached patches on E9 neurons depolar ized by bath application of 145 mM KCl in the presence of 5 mM external Ca2 +. However, BK channels were activated immediately by this procedure and we re detected at a higher density in TGF beta 1-treated cells. In addition, a nalyses of macroscopic K-Ca fluctuations, and the voltage-dependence of K-C a tail currents, suggest that IK channels do not contribute to voltage-evok ed whole cell K-Ca. IK channels therefore may have some other function. The se results indicate that the effects of TGF beta 1 on CG neurons entail dis tinct actions on multiple K-Ca channel subtypes.