Differential regulation of the two components of voltage-activated
outward potassium current in human atrial myocytes during serum
-stimulated growth.
Hatem, St[acute]ephane N., Agn[grave]es B[acute]enardeau, Catherine
R[umlaut]ucker-Martin, Jane-Lyse Samuel, Edouard Coraboeuf, and Jean
-Jacques Mercadier.
Laboratoire de Cardiologie Mol[acute]eculaire et Cellulaire,
Universit[acute]e de Paris XI - C.N.R.S. URA 1159,
H[circumflex]opital Marie Lannelongue, Le Plessis Robinson, France,
INSERM U 127, H[circumflex]opital Lariboisi[grave]ere, Paris,
France
APStracts 3:0191H, 1996.
To examine whether the two components of the voltage-activated outward
K+ current, Ito1 and Isus, in human atrial myocytes are distinct
currents differentially regulated, we studied their behavior during
serum-induced growth of cultured myocytes. Currents were recorded in
whole-cell patch-clamped myocytes. After a week in culture (day 8)
membrane capacitance was twice the value in freshly dissociated
myocytes (178.7+/-23 vs 83.1+/-5.5 pF, p<0.001). Ito1 density
did not differ from that in freshly dissociated myocytes (at +40 mV:
4.38+/-0.8 pA/pF vs 3.71+/-0.6 pA/pF), whereas that of Isus was
markedly increased (at +40 mV: 9.76+/-2 pA/pF vs 2.21+/-0.29 pA/pF,
p<0.001). Following inactivation of Ito1 by a prepulse,
sustained depolarization elicited in cultured myocytes an Isus with a
density of 10.22+/-1.18 pA/pF and an apparent tail current reversal
potential of -73.5+/-3.2 mV, indicating high K+ selectivity. Isus was
highly sensitive to 4-AP (55.4+/-4.4% inhibition in 50 [mu]M 4-AP)
and to D600, with an IC50 of 34.2 x 10-6 M. Addition of 5-10 nM
staurosporine at day 3 prevented cell growth and reduced Ito1 density
but not the increase in Isus density which was inhibited by 10 [mu]M
staurosporine. Our results indicate that Ito1 and Isus are regulated
independently during in vitro myocyte growth in human atrial myocytes
and that the increase in Isus density is not mediated by a protein
kinase C dependent pathway.
Received 11 August 1995; accepted in final form 27 March 1996.
APS Manuscript Number H754-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 May 96