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Active Ca²⁺ channels, according to Hudmon et al. (page 537), get their own dedicated Ca²⁺ sensors that cause well-used channels to open with gusto.

Some Ca²⁺ channels, including voltage-gated L-type channels, let through more Ca²⁺ per opening when they are used frequently. This positive feedback, known as facilitation, allows fast-beating cardiac cells, for instance, to beat harder (as during exercise). The new findings reveal that local retention of a Ca²⁺/calmodulin-dependent kinase, CaMKII, is behind this ability.

CaMKII is activated by autophosphorylation in response to Ca²⁺/calmodulin. The authors find that CaMKII then tethers itself to the pore-forming _1C subunit of the L-type channel, which is abundant in heart muscle. Even upon dephosphorylation, CaMKII lingers at the channel.

From this position, the kinase can up-regulate channel activity when Ca²⁺ influx is frequent. The authors show that active CaMKII phosphorylates two regions of _1C that were previously found to regulate channel activity. Unlike NMDAR-bound CaMKII, which is constitutively active, _1C-bound CaMKII still depends on Ca²⁺/calmodulin. This difference might explain why NMDARs are up-regulated for the long term by a brief stimulus, whereas full activity of voltage-gated channels requires repeated activation.

Tethering to _1C is necessary for facilitation, even though the channel can be phosphorylated by free kinase. The close proximity may allow the kinase to outdo channel-defacilitating phosphatases. Only when Ca²⁺ influx is frequent, and CaMKII activity is repeatedly high, can CaMKII win the fight.

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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Related Article

CaMKII tethers to L-type Ca²⁺ channels, establishing a local and dedicated integrator of Ca²⁺ signals for facilitation

Andy Hudmon, Howard Schulman, James Kim, Janet M. Maltez, Richard W. Tsien, and Geoffrey S. Pitt
J. Cell Biol. 2005 171: 537-547. [Abstract] [Full Text] [PDF]

This Article PDF (Full Text) Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Related Collections Related Article Social Bookmarking                      What's this?