Coexpression and stimulation of parathyroid hormone receptor positively regulates slowly activating IsK channels expressed in Xenopus oocytes.
Expression of the IsK protein in Xenopus oocytes induced the characteristically slow, voltage-dependent outward currents. Superfusion with the parathyroid hormone (PTH) peptide 1-34 had no effect on IsK when expressed alone, but increased IsK when IsK was coexpressed with the PTH-receptor. PTH receptor stimulation caused a shift of IsK conductance-voltage relationship to more negative potentials, and a decrease of both the rate of IsK activation and deactivation. IsK regulation by PTH was independent of extracellular Ca2+, and was also present IsK protein mutants lacking the protein kinase C consensus site. However, regulation of IsK by PTH was mimicked by activators of protein kinase A (PKA) and greatly reduced in the presence of the kinase inhibitors staurosporine and H89. These results suggest that PTH regulates IsK by a mechanism involving phosphorylation independent of protein kinase C (PKC). Such regulation may play a role in proximal tubule cells of the kidney, where both PTH receptor and the IsK protein are expressed.
Waldegger
S
S
Institute of Physiology, Eberhard-Karls-Universität Tübingen, Germany.
Raber
G
G
Süssbrich
H
H
Ruppersberg
J P
JP
Fakler
B
B
Murer
H
H
Lang
F
F
Busch
A E
AE
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D005260:Female; D008564:Membrane Potentials; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011494:Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D018016:Receptors, Parathyroid Hormone / Q000187:drug effects / Q000378:metabolism*; D013268:Stimulation, Chemical; D014982:Xenopus laevis
D015220:Calcium Channels; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D018016:Receptors, Parathyroid Hormone; C059983:potassium channel protein I(sk); D011494:Protein Kinases