Single-channel activity of the Ca2+-dependent K+ channel is modulated by FK506 and rapamycin.
Single-channel patch clamp recordings were performed in primary cultured neurons from rat dorsal hippocampi. Ca2+-dependent and TEA-sensitive K+ current was recorded from the neurons. Application of immunosuppressants FK506 and rapamycin to the channel inside the plasma membrane of the neurons significantly prolonged the mean open time of the channel. Calcineurin autoinhibitory fragment and W-7 induced no significant alteration in the mean open time of the channel. These results suggest that modulation of the activity of the Ca2+-dependent K+ channel by FK506 and rapamycin is directly through association of immunosuppressants with FKBP12.
Terashima
A
A
Hyogo Institute for Aging Brain and Cognitive Disorders, Saisho-Kou 520, Himeji 670-0981, Japan.
Nakai
M
M
Hashimoto
T
T
Kawamata
T
T
Taniguchi
T
T
Yasuda
M
M
Maeda
K
K
Tanaka
C
C
D000818:Animals; D065095:Calcineurin Inhibitors; D002118:Calcium / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology; D004553:Electric Conductivity; D006360:Heat-Shock Proteins / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011090:Polyenes / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats / Q000196:embryology; D020123:Sirolimus; D016559:Tacrolimus / Q000494:pharmacology*; D022021:Tacrolimus Binding Proteins; D019789:Tetraethylammonium / Q000494:pharmacology
D065095:Calcineurin Inhibitors; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D007166:Immunosuppressive Agents; D011090:Polyenes; D015221:Potassium Channels; D019789:Tetraethylammonium; D022021:Tacrolimus Binding Proteins; D002118:Calcium; D020123:Sirolimus; D016559:Tacrolimus