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Dual role of calmodulin in excitable cells

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Abstract

Consideration of the enzymatic reactions governing calcium channel phosphorylation and dephosphorylation leads one to deduce that there exist separate groups of enzymes, membrane-bound and cytoplasmic, that are activated by a common mediator, calmodulin (CaM), whose time-dependent appearance (via diffusion) at both locales is controlled by both intracellular calcium levels and electrostatic interaction with the membrane. In brief, the change in the sign and extent of the electrical charge borne by the modulator in the presence of calcium (Ca) brings about the electrostatic attraction that enables the transport of [Ca−CaM] to the membrane. This translocation of Ca−CaM makes possible a sequential activation of cellular enzymes whose locations differ. The sequence, both spatial and temporal, of the activation of various cellular enzymes by Ca−CaM appears to be a control network shared in common by excitable cells containing a stimulus-response pathway mediated by second messengers.

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Abbreviations

cAMP:

cyclic adenosine monophosphate

AC:

adenylate cyclase

PDE:

cyclic nucleotide phosphodiesterase

PPT:

phosphatase

Ca:

calcium ion

CaM:

calmodulin

Ca−CaM, Ca4CaM:

calcium-calmodulin complex

[Ca4CaM]m :

concentration of [Ca4CaM] in membrane vicinity

[Ca4CaM]m,dias :

concentration of [Ca4CaM] in membrane vicinity during diastole

[Ca4CaM]m,sys :

concentration of [Ca4CaM] in membrane vicinity during systole

[Ca4CaM]c :

concentration of [Ca4CaM] in cytoplasm

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Vieth, W.R., Nho, K. & Kale, S. Dual role of calmodulin in excitable cells. Ann Biomed Eng 21, 669–677 (1993). https://doi.org/10.1007/BF02368646

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