Calcium sparklets regulate local and global calcium in murine arterial smooth muscle.

Imagen de Manuel F Navedo
TítuloCalcium sparklets regulate local and global calcium in murine arterial smooth muscle.
Publication TypeJournal Article
Year of Publication2007
AutoresAmberg, GC, Navedo, MF, Nieves-Cintrón, M, Molkentin, JD, Santana, LF
JournalJ Physiol
Volume579
IssuePt 1
Pagination187-201
Date Published2007 Feb 15
ISSN0022-3751
Palabras claveAnimals, Calcium, Calcium Channels, L-Type, Enzyme Inhibitors, Ion Channel Gating, Membrane Potentials, Mesenteric Arteries, Mice, Mice, Knockout, Muscle, Smooth, Vascular, Myocytes, Smooth Muscle, Patch-Clamp Techniques, Protein Kinase C-alpha, Rats, Rats, Sprague-Dawley, Sarcoplasmic Reticulum Calcium-Transporting ATPases, Thapsigargin, Vascular Resistance
Abstract

In arterial smooth muscle, protein kinase Calpha (PKCalpha) coerces discrete clusters of L-type Ca2+ channels to operate in a high open probability mode, resulting in subcellular domains of nearly continual Ca2+ influx called 'persistent Ca2+ sparklets'. Our previous work suggested that steady-state Ca2+ entry into arterial myocytes, and thus global [Ca2+]i, is regulated by Ca2+ influx through clusters of L-type Ca2+ channels operating in this persistently active mode in addition to openings of solitary channels functioning in a low-activity mode. Here, we provide the first direct evidence supporting this 'Ca2+ sparklet' model of Ca2+ influx at a physiological membrane potential and external Ca2+ concentration. In support of this model, we found that persistent Ca2+ sparklets produced local and global elevations in [Ca2+]i. Membrane depolarization increased Ca2+ influx via low-activity and high-activity persistent Ca2+ sparklets. Our data indicate that Ca2+ entering arterial smooth muscle through persistent Ca2+ sparklets accounts for approximately 50% of the total dihydropyridine-sensitive (i.e. L-type Ca2+ channel) Ca2+ influx at a physiologically relevant membrane potential (-40 mV) and external Ca2+ concentration (2 mm). Consistent with this, inhibition of basal PKCalpha-dependent persistent Ca2+ sparklets decreased [Ca2+]i by about 50% in isolated arterial myocytes and intact pressurized arteries. Taken together, these data support the conclusion that in arterial smooth muscle steady-state Ca2+ entry and global [Ca2+]i are regulated by low-activity and PKCalpha-dependent high-activity persistent Ca(2+) sparklets.

DOI10.1113/jphysiol.2006.124420
Alternate JournalJ. Physiol. (Lond.)
PubMed ID17158168
PubMed Central IDPMC2075382
Grant ListHL077115 / HL / NHLBI NIH HHS / United States
HL07828 / HL / NHLBI NIH HHS / United States
HL085870 / HL / NHLBI NIH HHS / United States