| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Internal Medicine 2 Department of Molecular Physiology and Biophysics 3 Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232-6300, USA
L-type Ca2+ current (ICa-L) triggers Ca2+ release from the sarcoplasmic reticulum (SR) and both SR and ICa-L are potential sources of intracellular Ca2+ (Ca2+i) for feedback regulation of ICa-L. Ca2+i bound to calmodulin (Ca2+–CaM) can inhibit ICa-L, while Ca2+–CaM can also activate Ca2+–CaM-dependent protein kinase II (CaMK) to increase ICa. However, it is not known whether ICa-L or the SR is the primary source of Ca2+ for ICa-L regulation. The L-type Ca2+ channel C terminus is implicated as a critical transduction element for ICa-L responses to Ca2+–CaM and CaMK, and the C terminus undergoes voltage-dependent steric changes, suggesting that Ca2+i control of ICa-L may also be regulated by cell membrane potential. We developed conditions to separately test the relationship of Ca2+–CaM and CaMK to ICa-L and SR Ca2+i release during voltage clamp conditions modelled upon time and voltage domains relevant to the cardiac action potential. Here we show that CaMK increases ICa-L after brief positive conditioning pulses, whereas Ca2+–CaM reduces ICa-L over a broad range of positive and negative conditioning potentials. SR Ca2+ release was required for both Ca2+–CaM and CaMK ICa-L responses after strongly positive conditioning pulses (+10 and +40 mV), while Ca2+i from ICa-L was sufficient for Ca2+–CaM during weaker depolarizations. These findings show that ICa-L responses to CaMK are voltage dependent and suggest a new model of L-type Ca2+ channel regulation where voltage-dependent changes control ICa-L responses to Ca2+–CaM and CaMK signalling.
(Received 12 August 2003;
accepted after revision 27 October 2003;
first published online 31 October 2003)
Corresponding author M. E. Anderson: 383 Preston Research Building, Vanderbilt University Medical Center, Nashville, TN 37232-6300, USA. Email: mark.anderson{at}vanderbilt.edu
This article has been cited by other articles:
|
|
 |
|
  L. F. Couchonnal and M. E. Anderson The Role of Calmodulin Kinase II in Myocardial Physiology and Disease Physiology, June 1, 2008; 23(3): 151 - 159. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Bito, F. R. Heinzel, L. Biesmans, G. Antoons, and K. R. Sipido Crosstalk between L-type Ca2+ channels and the sarcoplasmic reticulum: alterations during cardiac remodelling Cardiovasc Res, January 15, 2008; 77(2): 315 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Anderson Multiple downstream proarrhythmic targets for calmodulin kinase II: Moving beyond an ion channel-centric focus Cardiovasc Res, March 1, 2007; 73(4): 657 - 666. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Litwin "Ryanogate": Who Leaked the Calcium? Circ. Res., February 3, 2006; 98(2): 165 - 168. [Full Text] [PDF]
|
|
|
|
 |
|
 D. B. Halling, P. Aracena-Parks, and S. L. Hamilton Regulation of Voltage-Gated Ca2+ Channels by Calmodulin Sci. Signal., December 20, 2005; 2005(315): re15 - re15. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Xiong, Q. K. Kleerekoper, R. He, J. A. Putkey, and S. L. Hamilton Sites on Calmodulin That Interact with the C-terminal Tail of Cav1.2 Channel J. Biol. Chem., February 25, 2005; 280(8): 7070 - 7079. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
