Calcium Regulation of Ion Channels

Swandulla, Dieter; Zeilhofer, Hanns Ulrich

doi:10.1007/978-1-4899-1901-4_5

Integrative Aspects of Calcium Signalling 1998

DOI: 10.1007/978-1-4899-1901-4_5

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Calcium Regulation of Ion Channels

Dieter Swandulla

Hanns Ulrich Zeilhofer

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1999

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“…The activity of these Ca 2ϩ channels is effectively regulated by G-protein-coupled receptors and by Ca 2ϩ -and voltage-dependent inactivation of these ion channels. 3,13,40 Among the different types of Ca 2ϩ channels, Ca 2ϩ -dependent inactivation is best documented for L-type Ca 2ϩ channels. 2,23,24,34,46 However, a Ca 2ϩ -mediated component of Ca 2ϩ channel inactivation has also been described for N-type channels (e.g., Ref.…”

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confidence: 99%

Calcium-dependent inactivation of neuronal calcium channel currents is independent of calcineurin

Zeilhofer¹,

Blank

Neuhuber

et al. 1999

Neuroscience

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Abstract-Dephosphorylation by the Ca 2ϩ /calmodulin-dependent phosphatase calcineurin has been suggested as an important mechanism of Ca 2ϩ -dependent inactivation of voltage-gated Ca 2ϩ channels. We have tested whether calcineurin plays a role in the inactivation process of two types of high-voltage-activated Ca 2ϩ channels (L and N type) widely expressed in the central nervous system, using the immunosuppressive drug FK506 (tacrolimus), which inhibits calcineurin after binding to intracellular FK506 binding proteins. Inactivation of L-and N-type Ca 2ϩ channels was studied in a rat pituitary tumor cell line (GH 3 ) and chicken dorsal root ganglion neurons, respectively. With the use of antisera directed against the calcineurin subunit B and the 12,000 mol. wt binding protein, we show that both proteins are present in the cytoplasm of GH 3 cells and chicken dorsal root ganglion neurons. Ionic currents through voltage-gated Ca 2ϩ channels were investigated in the perforated-patch and whole-cell configurations of the patch-clamp technique. The inactivation of L-as well as N-type Ca 2ϩ currents could be well fitted with a bi-exponential function. Inactivation was largely reduced when Ba 2ϩ substituted for extracellular Ca 2ϩ or when the Ca 2ϩ chelator EGTA was present intracellularly, indicating that both types of Ca 2ϩ currents exhibited Ca 2ϩ -dependent inactivation. Extracellular (perforated-patch configuration) or intracellular (whole-cell configuration) application of FK506 to inactivate calcineurin had no effect on the amplitude and time-course of Ca 2ϩ channel current inactivation of either L-or N-type Ca 2ϩ channels. In addition, we found that recovery from inactivation and rundown of N-type Ca 2ϩ channel currents were not affected by FK506.Our results provide direct evidence that the calcium-dependent enzyme calcineurin is not involved in the inactivation process of the two Ca 2ϩ channel types which are important for neuronal functioning, such as gene expression and transmitter release. ᭧ 1999 IBRO. Published by Elsevier Science Ltd.Key words: Ca 2ϩ channel, inactivation, calcineurin, FK506, FKBP.An increase in the intracellular concentration of free Ca 2ϩ ([Ca 2ϩ ] i ) plays a pivotal role in a large variety of physiological functions, such as excitation-secretion coupling and neuronal plasticity. On the other hand, excessive increases in [Ca 2ϩ ] i may lead to excitotoxic cell death, which occurs, for example, during brain ischemia and epileptic seizures. 16 In neurons, one important pathway that leads to an increase in [Ca 2ϩ ] i is the opening of voltage-gated Ca 2ϩ channels in the plasma membrane. The activity of these Ca 2ϩ channels is effectively regulated by G-protein-coupled receptors and by Ca 2ϩ -and voltage-dependent inactivation of these ion channels. 3,13,40 Among the different types of Ca 2ϩ channels, Ca 2ϩ -dependent inactivation is best documented for L-type Ca 2ϩ channels. 2,23,24,34,46 However, a Ca 2ϩ -mediated component of Ca 2ϩ channel inactivation has also been described for N-typ...

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mentioning

confidence: 99%

Calcium-dependent inactivation of neuronal calcium channel currents is independent of calcineurin

Zeilhofer¹,

Blank

Neuhuber

et al. 1999

Neuroscience

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Calcium Regulation of Ion Channels

Cited by 1 publication

References 133 publications

Calcium-dependent inactivation of neuronal calcium channel currents is independent of calcineurin

Calcium-dependent inactivation of neuronal calcium channel currents is independent of calcineurin

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