Bistability in the Ca(2+)/calmodulin-dependent protein kinase-phosphatase system
A mathematical model is presented of autophosphorylation of Ca(2+)/calmodulin-dependent protein kinase (CaMKII) and its dephosphorylation by a phosphatase. If the total concentration of CaMKII subunits is significantly higher than the phosphatase Michaelis constant, two stable steady states of the C...
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| Veröffentlicht in: | Biophysical journal 2000-11, Vol.79 (5), p.2211-2221 |
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| description | A mathematical model is presented of autophosphorylation of Ca(2+)/calmodulin-dependent protein kinase (CaMKII) and its dephosphorylation by a phosphatase. If the total concentration of CaMKII subunits is significantly higher than the phosphatase Michaelis constant, two stable steady states of the CaMKII autophosphorylation can exist in a Ca(2+) concentration range from below the resting value of the intracellular [Ca(2+)] to the threshold concentration for induction of long-term potentiation (LTP). Bistability is a robust phenomenon, it occurs over a wide range of parameters of the model. Ca(2+) transients that switch CaMKII from the low-phosphorylated state to the high-phosphorylated one are in the same range of amplitudes and frequencies as the Ca(2+) transients that induce LTP. These results show that the CaMKII-phosphatase bistability may play an important role in long-term synaptic modifications. They also suggest a plausible explanation for the very high concentrations of CaMKII found in postsynaptic densities of cerebral neurons. |
| doi_str_mv | 10.1016/S0006-3495(00)76469-1 |
| format | Article |
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If the total concentration of CaMKII subunits is significantly higher than the phosphatase Michaelis constant, two stable steady states of the CaMKII autophosphorylation can exist in a Ca(2+) concentration range from below the resting value of the intracellular [Ca(2+)] to the threshold concentration for induction of long-term potentiation (LTP). Bistability is a robust phenomenon, it occurs over a wide range of parameters of the model. Ca(2+) transients that switch CaMKII from the low-phosphorylated state to the high-phosphorylated one are in the same range of amplitudes and frequencies as the Ca(2+) transients that induce LTP. These results show that the CaMKII-phosphatase bistability may play an important role in long-term synaptic modifications. They also suggest a plausible explanation for the very high concentrations of CaMKII found in postsynaptic densities of cerebral neurons.</description><identifier>ISSN: 0006-3495</identifier><identifier>EISSN: 1542-0086</identifier><identifier>DOI: 10.1016/S0006-3495(00)76469-1</identifier><identifier>PMID: 11053103</identifier><language>eng</language><publisher>United States: Biophysical Society</publisher><subject>Animals ; Biochemistry ; Biophysical Phenomena ; Biophysics ; Brain - enzymology ; Calcium ; Calcium Signaling ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; Calcium-Calmodulin-Dependent Protein Kinases - chemistry ; Calcium-Calmodulin-Dependent Protein Kinases - genetics ; Calcium-Calmodulin-Dependent Protein Kinases - metabolism ; Enzyme Stability ; In Vitro Techniques ; Kinetics ; Long-Term Potentiation ; Mathematical models ; Models, Biological ; Mutagenesis, Site-Directed ; Neurology ; Phosphoprotein Phosphatases - chemistry ; Phosphoprotein Phosphatases - genetics ; Phosphoprotein Phosphatases - metabolism ; Phosphorylation ; Proteins ; Synapses - enzymology</subject><ispartof>Biophysical journal, 2000-11, Vol.79 (5), p.2211-2221</ispartof><rights>Copyright Biophysical Society Nov 2000</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1301111/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1301111/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11053103$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhabotinsky, A M</creatorcontrib><title>Bistability in the Ca(2+)/calmodulin-dependent protein kinase-phosphatase system</title><title>Biophysical journal</title><addtitle>Biophys J</addtitle><description>A mathematical model is presented of autophosphorylation of Ca(2+)/calmodulin-dependent protein kinase (CaMKII) and its dephosphorylation by a phosphatase. If the total concentration of CaMKII subunits is significantly higher than the phosphatase Michaelis constant, two stable steady states of the CaMKII autophosphorylation can exist in a Ca(2+) concentration range from below the resting value of the intracellular [Ca(2+)] to the threshold concentration for induction of long-term potentiation (LTP). Bistability is a robust phenomenon, it occurs over a wide range of parameters of the model. Ca(2+) transients that switch CaMKII from the low-phosphorylated state to the high-phosphorylated one are in the same range of amplitudes and frequencies as the Ca(2+) transients that induce LTP. These results show that the CaMKII-phosphatase bistability may play an important role in long-term synaptic modifications. They also suggest a plausible explanation for the very high concentrations of CaMKII found in postsynaptic densities of cerebral neurons.</description><subject>Animals</subject><subject>Biochemistry</subject><subject>Biophysical Phenomena</subject><subject>Biophysics</subject><subject>Brain - enzymology</subject><subject>Calcium</subject><subject>Calcium Signaling</subject><subject>Calcium-Calmodulin-Dependent Protein Kinase Type 2</subject><subject>Calcium-Calmodulin-Dependent Protein Kinases - chemistry</subject><subject>Calcium-Calmodulin-Dependent Protein Kinases - genetics</subject><subject>Calcium-Calmodulin-Dependent Protein Kinases - metabolism</subject><subject>Enzyme Stability</subject><subject>In Vitro Techniques</subject><subject>Kinetics</subject><subject>Long-Term Potentiation</subject><subject>Mathematical models</subject><subject>Models, Biological</subject><subject>Mutagenesis, Site-Directed</subject><subject>Neurology</subject><subject>Phosphoprotein Phosphatases - 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Participant titles)</collection><jtitle>Biophysical journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhabotinsky, A M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bistability in the Ca(2+)/calmodulin-dependent protein kinase-phosphatase system</atitle><jtitle>Biophysical journal</jtitle><addtitle>Biophys J</addtitle><date>2000-11-01</date><risdate>2000</risdate><volume>79</volume><issue>5</issue><spage>2211</spage><epage>2221</epage><pages>2211-2221</pages><issn>0006-3495</issn><eissn>1542-0086</eissn><abstract>A mathematical model is presented of autophosphorylation of Ca(2+)/calmodulin-dependent protein kinase (CaMKII) and its dephosphorylation by a phosphatase. If the total concentration of CaMKII subunits is significantly higher than the phosphatase Michaelis constant, two stable steady states of the CaMKII autophosphorylation can exist in a Ca(2+) concentration range from below the resting value of the intracellular [Ca(2+)] to the threshold concentration for induction of long-term potentiation (LTP). Bistability is a robust phenomenon, it occurs over a wide range of parameters of the model. Ca(2+) transients that switch CaMKII from the low-phosphorylated state to the high-phosphorylated one are in the same range of amplitudes and frequencies as the Ca(2+) transients that induce LTP. These results show that the CaMKII-phosphatase bistability may play an important role in long-term synaptic modifications. 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| subjects | Animals Biochemistry Biophysical Phenomena Biophysics Brain - enzymology Calcium Calcium Signaling Calcium-Calmodulin-Dependent Protein Kinase Type 2 Calcium-Calmodulin-Dependent Protein Kinases - chemistry Calcium-Calmodulin-Dependent Protein Kinases - genetics Calcium-Calmodulin-Dependent Protein Kinases - metabolism Enzyme Stability In Vitro Techniques Kinetics Long-Term Potentiation Mathematical models Models, Biological Mutagenesis, Site-Directed Neurology Phosphoprotein Phosphatases - chemistry Phosphoprotein Phosphatases - genetics Phosphoprotein Phosphatases - metabolism Phosphorylation Proteins Synapses - enzymology |
| title | Bistability in the Ca(2+)/calmodulin-dependent protein kinase-phosphatase system |
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