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(Circulation Research. 1997;80:345-353.)
© 1997 American Heart Association, Inc.

Articles

Different Compartments of Sarcoplasmic Reticulum Participate in the Excitation-Contraction Coupling Process in Human Atrial Myocytes

Stephane N. Hatem, Agnes Benardeau, Catherine Rucker-Martin, Isabelle Marty, Patricia de Chamisso, Michel Villaz, Jean-Jacques Mercadier

the Laboratoire de Cardiologie Moleculaire et Cellulaire (S.N.H., A.B., C.R.-M., J.-J.M.), Universite de Paris XI-CNRS URA 1159, Hopital Marie Lannelongue, Le Plessis Robinson, France; the Laboratoire de Biophysique Moleculaire et Cellulaire (I.M., M.V.), Grenoble, France; and the Laboratoire de Cancerologie Experimentale (P. de C.), CEA, Fontenay-aux-Roses, France.

Correspondence to Dr J.-J. Mercadier, CNRS-URA 1159, Hopital Marie Lannelongue, 133 Avenue de la Resistance, 92350 Le Plessis Robinson, France. E-mail jjmercad@pratique.fr

The excitation-contraction coupling process of human atrial myocytes was studied in voltage-clamped myocytes isolated from right atrial appendages obtained during cardiac surgery. Intracellular Ca²⁺ transients (Ca_i transients) were monitored with 0.1 mmol/L indo 1 added to the internal dialyzing solution. Ryanodine receptors (RyRs) and sarcomeric -actinin were stained with specific antibodies and visualized using plane and confocal microscopy. L-Type Ca²⁺ current (I_Ca) elicited a prolonged Ca_i transient, with an initial rapidly activating phase (slope 1, 23.6±1.2 s^-1) followed by a slowly activating phase (slope 2, 5.8±0.4 s^-1; P<.001 versus slope 1), resulting in a dome-shaped Ca_i transient. Ryanodine (100 µmol/L) inhibited 79±6% of the Ca_i transient, indicating that it was due essentially to sarcoplasmic reticulum Ca²⁺ release. During step depolarizations, maximal activation of the Ca_i transient or tail current (I_tail) (in cells dialyzed with Ca²⁺ buffer–free internal solution) preceded that of I_Ca and did not follow its voltage dependence (n=12). Test pulses lasting from 5 to 150 milliseconds elicited a similar time course of both Ca_i transient and I_tail (n=5). In a given cell, the two components of the Ca_i transient could be dissociated by altering the intracellular Ca²⁺ load, by increasing the stimulation rate from 0.1 to 1 Hz, or by varying the amplitude of I_Ca. Immunostaining of atrial sections and isolated myocytes showed that a large number of RyRs were located not only in a subsarcolemmal position but also deeper inside the cell, in a regularly spaced transverse band pattern at the level of Z lines. Together, our results indicate that, in human atrial myocytes, I_Ca only partially controls the activation of RyRs, with the prolonged and dome-shaped Ca_i transient of these cells probably reflecting the activation of RyRs not coupled to L-type Ca²⁺ channels.

Key Words: intracellular Ca²⁺ transient • sarcoplasmic reticulum • human cardiac myocyte

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