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Regulation of junctional and non‐junctional sarcoplasmic reticulum calcium release in excitation‐contraction coupling in cat atrial myocytes
Author(s) -
Sheehan Katherine A.,
Blatter Lothar A.
Publication year - 2003
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2002.026963
Subject(s) - ryanodine receptor , calcium , chemistry , biophysics , depolarization , egta , endoplasmic reticulum , medicine , biochemistry , biology , organic chemistry
We have characterized the dependence on membrane potential ( V m ) and calcium current ( I Ca ) of calcium‐induced calcium release (CICR) from the junctional‐SR (j‐SR, in the subsarcolemmal (SS) space) and non‐junctional‐SR (nj‐SR, in the central (CT) region of the cell) of cat atrial myocytes using whole‐cell voltage‐clamp together with spatially resolved laser‐scanning confocal microscopy. Subsarcolemmal and central [Ca 2+ ] i transient amplitudes and I Ca had a bell‐shaped dependence on V m , but [Ca 2+ ] i reached a maximum at more negative V m (‐10 to 0 mV) than I Ca (+10 mV). Termination of I Ca after a brief depolarization (2.5 to 22.5 ms) immediately interrupted only the SS [Ca 2+ ] i transient, leaving the development of the CT [Ca 2+ ] i transient unaffected. Block of SR function with 20 μ m ryanodine and 2 μ m thapsigargin, revealed that > 90 % of the control [Ca 2+ ] i transient amplitude was attributable to active SR Ca 2+ release through ryanodine receptors (RyRs). The gain of SR Ca 2+ release was highest in the SS space at negative test potentials and was less pronounced in the CT region. Inhibition of Na + ‐Ca 2+ exchange resulted in prolonged and higher amplitude [Ca 2+ ] i transients, elevated resting [Ca 2+ ] i , accelerated propagation of CICR, decreased extrusion of Ca 2+ and an increase in j‐SR Ca 2+ load. Increasing the cytosolic Ca 2+ buffer capacity by internal perfusion with 1 m m EGTA limited SR Ca 2+ release to the SS region, indicating that Ca 2+ release from nj‐SR is initiated by diffusion of Ca 2+ from the cell periphery and propagating CICR. Junctional‐SR Ca 2+ release occurred at discrete sites whose order of activation and amplitude of release varied from beat to beat. In conclusion, during normal excitation‐contraction coupling in cat atrial myocytes, only Ca 2+ release from the j‐SR is directly activated by Ca 2+ entering via I Ca . Elevation of SS [Ca 2+ ] i is required to provide the cytosolic Ca 2+ gradient needed to initiate regenerative and propagating CICR from nj‐SR.