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

Gregory C. Amberg, Manuel F. Navedo, Madeline Nieves-cintrón, Jeffery D. Molkentin, Luis F. Santana

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

In arterial smooth muscle, protein kinase Cα (PKCα) 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 PKCα-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 PKCα-dependent high-activity persistent Ca2+ sparklets.

Original languageEnglish (US)
Pages (from-to)187-201
Number of pages15
JournalJournal of Physiology
Volume579
Issue number1
DOIs
StatePublished - Feb 15 2007
Externally publishedYes

ASJC Scopus subject areas

  • Physiology

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