Novel regulation of the A-type K+ current in murine proximal colon by calcium-calmodulin-dependent protein kinase II.
1. The kinetics of inactivation of delayed rectifier K+ current in murine colonic myocytes differed in amphotericin-permeabilized patch and conventional patch clamp. The difference was accounted for by Ca2+ buffering. 2. Calcium-calmodulin-dependent protein kinase II (CaMKII) inhibitors increased the rate of inactivation and slowed recovery from inactivation of the outward current. This was seen in single steps and in the envelope of the current tails. The effect was largely on the TEA-insensitive component of current. 3. Dialysis of myocytes with autothiophosphorylated CaMKII slowed inactivation. This effect was reversed by addition of CaMKII inhibitor. 4. Antibodies revealed CaMKII-like immunoreactivity in murine colonic myocytes and other cells. Immunoblots identified a small protein with CaMKII-like immunoreactivity in homogenates of colonic muscle. 5. We conclude that CaMKII regulates delayed rectifier K+ currents in murine colonic myocytes. The changes in the delayed rectifier current may participate in the Ca2+-dependent regulation of gastrointestinal motility.
Koh
S D
SD
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA. skoh@physio.unr.edu
Perrino
B A
BA
Hatton
W J
WJ
Kenyon
J L
JL
Sanders
K M
KM
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003106:Colon / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000502:physiology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009130:Muscle, Smooth / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D000096926:Benzenesulfonamides
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D001596:Benzylamines; D002118:Calcium; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D004791:Enzyme Inhibitors; D011188:Potassium; D013449:Sulfonamides; C072105:KN 93; D000096926:Benzenesulfonamides; C063302:KN 62