Calcium sparklets regulate local and global calcium in murine arterial smooth muscle.
Submitted by Manuel F Navedo on
Title | Calcium sparklets regulate local and global calcium in murine arterial smooth muscle. |
Publication Type | Journal Article |
Year of Publication | 2007 |
Authors | Amberg, GC, Navedo, MF, Nieves-Cintrón, M, Molkentin, JD, Santana, LF |
Journal | J Physiol |
Volume | 579 |
Issue | Pt 1 |
Pagination | 187-201 |
Date Published | 2007 Feb 15 |
ISSN | 0022-3751 |
Keywords | Animals, 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. |
DOI | 10.1113/jphysiol.2006.124420 |
Alternate Journal | J. Physiol. (Lond.) |
PubMed ID | 17158168 |
PubMed Central ID | PMC2075382 |
Grant List | HL077115 / HL / NHLBI NIH HHS / United States HL07828 / HL / NHLBI NIH HHS / United States HL085870 / HL / NHLBI NIH HHS / United States |