HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 572/3/799    most recent jphysiol.2005.103267v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sheehan, K. A. Articles by Blatter, L. A. Search for Related Content PubMed PubMed Citation Articles by Sheehan, K. A. Articles by Blatter, L. A. Related Collections Cardiovascular

¹ Department of Physiology, Loyola University Chicago, Maywood, IL 60153, USA

Calcium sparks result from the concerted opening of a small number of Ca²⁺ release channels (ryanodine receptors, RyRs) organized in clusters in the membrane of the sarcoplasmic reticulum (SR). Calcium sparks represent the elementary events of SR Ca²⁺ release in cardiac myocytes, and their spatial and temporal summation results in whole-cell [Ca²⁺]_i transients observed during excitation–contraction coupling (ECC). Atrial myocytes generally lack transverse tubules; however, during ECC Ca²⁺ release is initiated from junctional SR (j-SR) in the cell periphery from where activation propagates inwardly through Ca²⁺-induced Ca²⁺ release (CICR) from non-junctional SR (nj-SR). Despite the structural differences in the microdomains of RyRs of j-SR and nj-SR, spontaneous Ca²⁺ sparks are observed from both types of SR, albeit at different frequencies. In cells that showed spontaneous Ca²⁺ sparks from j-SR and nj-SR, subsarcolemmal (SS) Ca²⁺ sparks from the j-SR were 3–4 times more frequent than central (CTR) Ca²⁺ sparks occurring from nj-SR. Subsarcolemmal Ca²⁺ sparks had a slightly higher amplitude, but were essentially identical in their spatial spread and duration when compared to CTR Ca²⁺ sparks. Sensitization of RyRs with a low concentration (0.1 mM) of caffeine led to a 107% increase in the frequency of CTR Ca²⁺ sparks, whereas the SS Ca²⁺ spark frequency increased by only 58%, suggesting that the nj-SR is capable of much higher Ca²⁺ spark activity than observed normally in unstimulated cells. The L-type Ca²⁺ channel blocker verapamil reduced SS Ca²⁺ spark frequency to 38% of control values, whereas Ca²⁺ spark activity from nj-SR was reduced by only 19%, suggesting that SS Ca²⁺ sparks are under the control of Ca²⁺ influx from the extracellular space. Removal of extracellular Ca²⁺ eliminated SS Ca²⁺ sparks completely, whereas Ca²⁺ sparks from the nj-SR continued, albeit at a lower frequency. In membrane-permeabilized (saponin-treated) atrial myocytes, where [Ca²⁺] can be experimentally controlled throughout the entire myocyte, j-SR and nj-SR Ca²⁺ spark frequencies were identical, and Ca²⁺ sparks could be observed spaced at sarcomeric distances throughout the entire cell, suggesting that all release sites of the nj-SR can become active. Measurement of SR Ca²⁺ load (10 mM caffeine) revealed no difference between j-SR and nj-SR. The data suggest that in atrial myocytes, which lack a t-tubular system, the nj-SR is fully equipped with a three-dimensional array of functional SR Ca²⁺ release sites; however, in intact cells under resting conditions, peripheral RyR clusters have a higher probability of activation owing to their association with surface membrane Ca²⁺ channels, leading to higher spontaneous Ca²⁺ spark activity. In conclusion, Ca²⁺ sparks originating from both j-SR and nj-SR are rather stereotypical and show little differences in their spatiotemporal properties. In intact cells, however, the higher frequency of spontaneous SS Ca²⁺ sparks arises from the structural arrangement of sarcolemma and j-SR membrane and thus from the difference in the trigger mechanism.

(Received 8 December 2005; accepted after revision 12 February 2006; first published online 16 February 2006)
Corresponding author L. A. Blatter: Department of Physiology, Loyola University Chicago, 2160 S. First Avenue, Maywood, IL 60153, USA. Email: lblatte{at}lumc.edu

This article has been cited by other articles:

				M. Hirose, B. D. Stuyvers, W. Dun, H. E.D.J. ter Keurs, and P. A. Boyden Function of Ca2+ Release Channels in Purkinje Cells That Survive in the Infarcted Canine Heart: A Mechanism for Triggered Purkinje Ectopy Circ Arrhythmia Electrophysiol, December 1, 2008; 1(5): 387 - 395. [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]

				V. Lukyanenko, A. Ziman, A. Lukyanenko, V. Salnikov, and W. J. Lederer Functional groups of ryanodine receptors in rat ventricular cells J. Physiol., August 15, 2007; 583(1): 251 - 269. [Abstract] [Full Text] [PDF]

				H. E. D. J. ter Keurs and P. A. Boyden Calcium and Arrhythmogenesis Physiol Rev, April 1, 2007; 87(2): 457 - 506. [Abstract] [Full Text] [PDF]