TGFbeta1 regulates the gating properties of intermediate-conductance KCa channels in developing parasympathetic neurons.
The developmental expression of Ca2+-activated K+ channels (KCa) in chick ciliary ganglion (CG) neurons is regulated by a target-derived avian isoform of TGFbeta1, which evokes a robust increase in the number of functional large-conductance (BK) KCa channels but which produces no change in their kinetics. However, CG neurons express multiple KCa channel subtypes. Here we show that TGFbeta1 regulates the gating properties of intermediate-conductance (IK) KCa channels in developing CG neurons. IK channels in inside-out patches excised from control E9 CG neurons became active on exposure to 1-5 microM free Ca2+ but then remained active on return to Ca2+-free salines. In contrast, IK channels in TGFbeta1-treated cells became active on exposure to 1-5 microM Ca2+, but became quiescent immediately on return to Ca2+-free salines. In contrast to its effects on BK channels, TGFbeta1 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 depolarized 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 were detected at a higher density in TGFbeta1-treated cells. In addition, analyses of macroscopic KCa fluctuations, and the voltage-dependence of KCa tail currents, suggest that IK channels do not contribute to voltage-evoked whole cell KCa. IK channels therefore may have some other function. These results indicate that the effects of TGFbeta1 on CG neurons entail distinct actions on multiple KCa channel subtypes.
Lhuillier
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Department of Biology and Biochemistry, University of Houston, Houston, Texas 77204-5513, USA.
Dryer
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SE
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002460:Cell Line; D002642:Chick Embryo / Q000166:cytology / Q000502:physiology; D004553:Electric Conductivity; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010275:Parasympathetic Nervous System / Q000196:embryology*; D015221:Potassium Channels / Q000502:physiology*; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta / Q000502:physiology*
D015221:Potassium Channels; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D002118:Calcium