Modulation of the cloned skeletal muscle L-type Ca2+ channel by anchored cAMP-dependent protein kinase

Barry D. Johnson, Jeffrey P. Brousal, Blaise Peterson, Peter A. Gallombardo, Gregory H. Hockerman, Yvonne Lai, Todd Scheuer, William A. Catterall

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Abstract

Ca2+ influx through skeletal muscle Ca2+ channels and the force of contraction are increased in response to β-adrenergic stimulation and high- frequency electrical stimulation. These effects are thought to be mediated by cAMP-dependent phosphorylation of the skeletal muscle Ca2+ channel. Modulation of the cloned skeletal muscle Ca2+ channel by cAMP-dependent phosphorylation and by depolarizing prepulses was reconstituted by transient expression in tsA-201 cells and compared to modulation of the native skeletal muscle Ca2+ channel as expressed in mouse 129CB3 skeletal muscle cells. The heterologously expressed Ca2+ channel consisting of α1, α2δ, and β subunits gave currents that were similar in time course, current density, and dihydropyridine sensitivity to the native Ca2+ channel. cAMP dependent protein kinase (PKA) stimulation by Sp-5,6-DCI-cBIMPS (cBIMPS) increased currents through both native and expressed channels two- to fourfold. Tail currents after depolarizations to potentials between -20 and +80 mV increased in amplitude and decayed more slowly as either the duration or potential of the depolarization was increased. The time- and voltage-dependent slowing of channel deactivation required the activity of PKA, because it was enhanced by cBIMPS and reduced or eliminated by the peptide PKA inhibitor PKI (5-24) amide. This voltage-dependent modulation of the cloned skeletal muscle Ca2+ channel by PKA also required anchoring of PKA by A-Kinase Anchoring Proteins because it was blocked by peptide Ht 31, which disrupts such anchoring. The results show that the skeletal muscle Ca2+ channel expressed in heterologous cells is modulated by PKA at rest and during depolarization and that this modulation requires anchored protein kinase, as it does in native skeletal muscle cells.

Original languageEnglish (US)
Pages (from-to)1243-1255
Number of pages13
JournalJournal of Neuroscience
Volume17
Issue number4
Publication statusPublished - Feb 21 1997

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All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Johnson, B. D., Brousal, J. P., Peterson, B., Gallombardo, P. A., Hockerman, G. H., Lai, Y., ... Catterall, W. A. (1997). Modulation of the cloned skeletal muscle L-type Ca2+ channel by anchored cAMP-dependent protein kinase. Journal of Neuroscience, 17(4), 1243-1255.