PMID- 7937825
OWN - NLM
STAT- MEDLINE
DCOM- 19941027
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 91
IP  - 20
DP  - 1994 Sep 27
TI  - Dual regulation of Ca2+/calmodulin-dependent kinase II activity by membrane 
      voltage and by calcium influx.
PG  - 9659-63
AB  - Calcium entry through voltage-gated Ca2+ channels is critical in cardiac 
      excitation-contraction coupling and calcium metabolism. In this report, we 
      demonstrate both spatially resolved and temporally distinct effects of 
      Ca2+/calmodulin-dependent protein kinase II (CaMKII) on L-type Ca2+ channel 
      current (ICa) in rat cardiac myocytes. Either depolarization alone or calcium 
      influx can increase the amplitude and slow the inactivation of ICa. The distinct 
      voltage- and Ca(2+)-dependent effects persist with time constants of 
      approximately 1.7 sec and 9 sec, respectively. Both effects are completely 
      abolished by a specific peptide inhibitor of CaMKII. This CaMKII inhibitor also 
      suppresses the prolongation of ICa induced by depolarizing holding potentials. 
      Furthermore, using an antibody specific for the autophosphorylated (activated) 
      CaMKII, we find that this kinase is localized close to sarcolemmal membranes and 
      that the profile of CaMKII activation correlates qualitatively with the changes 
      in ICa under various conditions. Therefore, we conclude that the action of CaMKII 
      on ICa is dually regulated by membrane depolarization and by Ca2+ influx; the 
      latter directly activates CaMKII, whereas the former likely promotes the 
      interaction between constitutive CaMKII and the membrane-channel proteins. These 
      regulatory mechanisms provide positive-feedback control of Ca2+ channels and are 
      probably important in the regulation of cardiac contractility and other 
      intracellular Ca(2+)-regulated processes.
FAU - Xiao, R P
AU  - Xiao RP
AD  - Laboratory of Cardiovascular Science, Gerontology Research Center, National 
      Institute on Aging, National Institutes of Health, Baltimore, MD 21224.
FAU - Cheng, H
AU  - Cheng H
FAU - Lederer, W J
AU  - Lederer WJ
FAU - Suzuki, T
AU  - Suzuki T
FAU - Lakatta, E G
AU  - Lakatta EG
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Calcium Channels)
RN  - 0 (Isoenzymes)
RN  - 0 (Isoquinolines)
RN  - 0 (Piperazines)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Sulfonamides)
RN  - 25612-73-1 (Adenylyl Imidodiphosphate)
RN  - 526U7A2651 (Egtazic Acid)
RN  - 65595-90-6 (W 7)
RN  - 84477-87-2 (1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - K22DDW77C0 (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid)
RN  - L628TT009W (Isoproterenol)
RN  - N3D6TG58NI (Thioridazine)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
MH  - Adenylyl Imidodiphosphate/pharmacology
MH  - Animals
MH  - Calcium Channels/*physiology
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Cells, Cultured
MH  - Egtazic Acid/analogs & derivatives/pharmacology
MH  - Electric Conductivity
MH  - Electric Stimulation
MH  - Heart/drug effects/*physiology
MH  - Isoenzymes/metabolism
MH  - Isoproterenol/pharmacology
MH  - Isoquinolines/pharmacology
MH  - Kinetics
MH  - Membrane Potentials/drug effects
MH  - Myocardium/*enzymology
MH  - Norepinephrine/pharmacology
MH  - Piperazines/pharmacology
MH  - Protein Kinase Inhibitors
MH  - Rats
MH  - Sulfonamides/pharmacology
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Thioridazine/pharmacology
MH  - Time Factors
PMC - PMC44873
EDAT- 1994/09/27 00:00
MHDA- 1994/09/27 00:01
PMCR- 1995/03/27
CRDT- 1994/09/27 00:00
PHST- 1994/09/27 00:00 [pubmed]
PHST- 1994/09/27 00:01 [medline]
PHST- 1994/09/27 00:00 [entrez]
PHST- 1995/03/27 00:00 [pmc-release]
AID - 10.1073/pnas.91.20.9659 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9659-63. doi: 
      10.1073/pnas.91.20.9659.