| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Received November 6, 2006
Revised November 30, 2006
Accepted after revision November 30, 2006
1 University of Washington
2 Cincinnati Children's Hospital Medical Center
* To whom correspondence should be addressed. E-mail: santana{at}u.washington.edu.
In arterial smooth muscle, protein kinase C (PKC)
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 PKC-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 PKC-dependent, high activity, persistent Ca2+ sparklets.
This article has been cited by other articles:
|
|
 |
|
  M. J. Berridge Smooth muscle cell calcium activation mechanisms J. Physiol., November 1, 2008; 586(21): 5047 - 5061. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nieves-Cintron, G. C. Amberg, M. F. Navedo, J. D. Molkentin, and L. F. Santana The control of Ca2+ influx and NFATc3 signaling in arterial smooth muscle during hypertension PNAS, October 7, 2008; 105(40): 15623 - 15628. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Cheng and W. J. Lederer Calcium Sparks Physiol Rev, October 1, 2008; 88(4): 1491 - 1545. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. Navedo, M. Nieves-Cintron, G. C. Amberg, C. Yuan, V. S. Votaw, W. J. Lederer, G. S. McKnight, and L. F. Santana AKAP150 Is Required for Stuttering Persistent Ca2+ Sparklets and Angiotensin II-Induced Hypertension Circ. Res., February 1, 2008; 102(2): e1 - e11. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. F. Santana SMAKing Ca2+ sparks in arterial myocytes J. Physiol., October 1, 2007; 584(1): 1 - 1. [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. Navedo, G. C. Amberg, R. E. Westenbroek, M. J. Sinnegger-Brauns, W. A. Catterall, J. Striessnig, and L. F. Santana Cav1.3 channels produce persistent calcium sparklets, but Cav1.2 channels are responsible for sparklets in mouse arterial smooth muscle Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1359 - H1370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Jaggar Smooth muscle sparklet Cav channels defined: 1.2 is the number Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1317 - H1319. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
