Novel regulation of the A-type H+ current in murine proximal colon by calcium-calmodulin-dependent protein kinase II

1. The kinetics of inactivation of delayed rectifier K+ current in murine c olonic myocytes differed in amphotericin-permeabilized patch and convention al patch clamp. The difference was accounted for by Ca2+ buffering. 2. Calcium-calmodulin-dependent protein kinase II (CaMKII) inhibitors incre ased 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 c urrent tails. The effect was largely on the TEA-insensitive component of cu rrent. 3. Dialysis of myocytes with autothiophosphorylated CaMKII slowed inactivat ion. This effect was reversed by addition of CaMKII inhibitor: 4. Antibodies revealed CaMKII-like immunoreactivity in murine colonic myocy tes and other cells. Immunoblots identified a small protein with CaMKII-lik e immunoreactivity in homogenates of colonic muscle. 5. We conclude that CaMKII regulates delayed rectifier K+ currents in murin e colonic myocytes. The changes in the delayed rectifier current may partic ipate in the Ca2+ dependent regulation of gastrointestinal motility.