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

J Physiol. 2007 Feb 15;579(Pt 1):187-201. doi: 10.1113/jphysiol.2006.124420. Epub 2006 Dec 7.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channels, L-Type / physiology*
  • Enzyme Inhibitors / pharmacology
  • Ion Channel Gating / physiology*
  • Membrane Potentials / physiology
  • Mesenteric Arteries / cytology
  • Mesenteric Arteries / physiology
  • Mice
  • Mice, Knockout
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / physiology*
  • Myocytes, Smooth Muscle / enzymology
  • Patch-Clamp Techniques
  • Protein Kinase C-alpha / genetics
  • Protein Kinase C-alpha / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / antagonists & inhibitors
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism
  • Thapsigargin / pharmacology
  • Vascular Resistance / physiology


  • Calcium Channels, L-Type
  • Enzyme Inhibitors
  • Thapsigargin
  • Protein Kinase C-alpha
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Calcium