Calcium-dependent enhancement of calcium current in smooth muscle by calmodulin-dependent protein kinase II.
Calcium entry through voltage-activated Ca2+ channels is important in regulating many cellular functions. Activation of these channels in many cell types results in feedback regulation of channel activity. Mechanisms linking Ca2+ channel activity with its downregulation have been described, but little is known of the events responsible for the enhancement of Ca2+ current that in many cells follows Ca2+ channel activation and an increase in cytoplasmic Ca2+ concentration. Here we investigate how this positive feedback is achieved in single smooth muscle cells. We find that in these cells voltage-activated calcium current is persistently but reversibly enhanced after periods of activation. This persistent enhancement of the Ca2+ current is mediated by activation of calmodulin-dependent protein kinase II because it is blocked when either the rise in cytoplasmic Ca2+ is inhibited or activation of calmodulin-dependent protein kinase II is prevented by specific peptide inhibitors of calcium-calmodulin or calmodulin-dependent protein kinase II itself. This mechanism may be important in different forms of Ca2+ current potentiation, such as those that depend on prior Ca2+ channel activation or are a result of agonist-induced release of Ca2+ from internal stores.
McCarron
J G
JG
Biomedical Imaging Group, University of Massachusetts Medical Center, Worcester 01655.
McGeown
J G
JG
Reardon
S
S
Ikebe
M
M
Fay
F S
FS
Walsh
J V
JV
D000595:Amino Acid Sequence; D000818:Animals; D002024:Bufo marinus; D002118:Calcium / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D004553:Electric Conductivity; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000502:physiology*; D011494:Protein Kinases / Q000502:physiology*
D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium