Regulation of Cl- channels by multifunctional CaM kinase.
cAMP kinase has been shown to mediate the cAMP pathway for regulation of Cl- channels in lymphocytes, but the mediator of an alternative, Ca2+ pathway has not been identified. We show here that Ca2+ ionophore activates Cl- currents in cell-attached and whole-cell patch-clamp recordings of Jurkat T lymphocytes, but this activation is not direct. The effect of Ca2+ ionophore on whole-cell Cl- currents is inhibited by a specific peptide inhibitor of multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase). Furthermore, Cl- channels are activated in excised patches by purified CaM kinase in a fashion that mimics the effect of Ca2+ ionophore in cell-attached recordings. These results suggest that CaM kinase mediates the Ca2+ pathway of Cl- channel activation.
Nishimoto
I
I
Department of Medicine, Stanford University School of Medicine, California 94305.
Wagner
J A
JA
Schulman
H
H
Gardner
P
P
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002147:Calmodulin / Q000494:pharmacology; D002460:Cell Line; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000494:pharmacology / Q000502:physiology*
D002147:Calmodulin; D018118:Chloride Channels; D002712:Chlorides; D008565:Membrane Proteins; D047428:Protein Kinase Inhibitors; D000001:Calcimycin; D000255:Adenosine Triphosphate; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium