Dynamic regulation of β1 subunit trafficking controls vascular contractility

Marie Dennis Leo, John P. Bannister, Damodaran Narayanan, Anitha Nair, Jordan E. Grubbs, Kyle S. Gabrick, Frederick Boop, Jonathan Jaggar

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Ion channels composed of pore-forming and auxiliary subunits control physiological functions in virtually all cell types. A conventional view is that channels assemble with their auxiliary subunits before anterograde plasma membrane trafficking of the protein complex. Whether the multisubunit composition of surface channels is fixed following protein synthesis or flexible and open to acute and, potentially, rapid modulation to control activity and cellular excitability is unclear. Arterial smooth muscle cells (myocytes) express large-conductance Ca2+-activated potassium (BK) channel α and auxiliary β1 subunits that are functionally significant modulators of arterial contractility. Here, we show that native BKα subunits are primarily (95%) plasma membrane-localized in human and rat arterial myocytes. In contrast, only a small fraction (10%) of total β1 subunits are located at the cell surface. Immunofluorescence resonance energy transfer microscopy demonstrated that intracellular β1 subunits are stored within Rab11A-postive recycling endosomes. Nitric oxide (NO), acting via cGMP-dependent protein kinase, and cAMP-dependent pathways stimulated rapid (≤1 min) anterograde trafficking of β1 subunit-containing recycling endosomes, which increased surface β1 almost threefold. These β1 subunits associated with surface-resident BKα proteins, elevating channel Ca2+ sensitivity and activity. Our data also show that rapid β1 subunit anterograde trafficking is the primary mechanism by which NO activates myocyte BK channels and induces vasodilation. In summary, we show that rapid β1 subunit surface trafficking controls functional BK channel activity in arterial myocytes and vascular contractility. Conceivably, regulated auxiliary subunit trafficking may control ion channel activity in a wide variety of cell types.

Original languageEnglish (US)
Pages (from-to)2361-2366
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number6
DOIs
StatePublished - Feb 11 2014

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Large-Conductance Calcium-Activated Potassium Channels
Muscle Cells
Blood Vessels
Endosomes
Ion Channels
Smooth Muscle Myocytes
Nitric Oxide
Cell Membrane
Cyclic GMP-Dependent Protein Kinases
Potassium Channels
Energy Transfer
Vasodilation
Fluorescent Antibody Technique
Blood Proteins
Microscopy
Membrane Proteins
Proteins

All Science Journal Classification (ASJC) codes

  • General

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Dynamic regulation of β1 subunit trafficking controls vascular contractility. / Leo, Marie Dennis; Bannister, John P.; Narayanan, Damodaran; Nair, Anitha; Grubbs, Jordan E.; Gabrick, Kyle S.; Boop, Frederick; Jaggar, Jonathan.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 6, 11.02.2014, p. 2361-2366.

Research output: Contribution to journalArticle

Leo, Marie Dennis ; Bannister, John P. ; Narayanan, Damodaran ; Nair, Anitha ; Grubbs, Jordan E. ; Gabrick, Kyle S. ; Boop, Frederick ; Jaggar, Jonathan. / Dynamic regulation of β1 subunit trafficking controls vascular contractility. In: Proceedings of the National Academy of Sciences of the United States of America. 2014 ; Vol. 111, No. 6. pp. 2361-2366.
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