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 language | English (US) |
|---|---|
| Pages (from-to) | 187-201 |
| Number of pages | 15 |
| Journal | Journal of Physiology |
| Volume | 579 |
| Issue number | 1 |
| DOIs | |
| State | Published - Feb 15 2007 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Physiology
Cite this
Calcium sparklets regulate local and global calcium in murine arterial smooth muscle. / Amberg, Gregory C.; Navedo, Manuel F.; Nieves-cintrón, Madeline; Molkentin, Jeffery D.; Santana, Luis F.
In: Journal of Physiology, Vol. 579, No. 1, 15.02.2007, p. 187-201.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Calcium sparklets regulate local and global calcium in murine arterial smooth muscle
AU - Amberg, Gregory C.
AU - Navedo, Manuel F.
AU - Nieves-cintrón, Madeline
AU - Molkentin, Jeffery D.
AU - Santana, Luis F.
PY - 2007/2/15
Y1 - 2007/2/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33846946127&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33846946127&partnerID=8YFLogxK
U2 - 10.1113/jphysiol.2006.124420
DO - 10.1113/jphysiol.2006.124420
M3 - Article
C2 - 17158168
AN - SCOPUS:33846946127
VL - 579
SP - 187
EP - 201
JO - Journal of Physiology
JF - Journal of Physiology
SN - 0022-3751
IS - 1
ER -