TY - JOUR
T1 - Molecular components of transient outward potassium current in cultured neonatal rat ventricular myocytes
AU - Kassiri, Zamaneh
AU - Hajjar, Roger
AU - Backx, Peter H.
N1 - Funding Information:
Acknowledgements This study was supported by CIHR grant to P.H.B. Z.K. is funded by HSFC/CIHR partnership fund. P.H.B. is a Career Investigator of Heart and Stroke Foundation of Ontario and is the Director of the Heart and Stroke/Richard Lewar Center. We are grateful for support from the Heart and Stroke/Richard Lewar Center, University of Toronto.
PY - 2002
Y1 - 2002
N2 - We have previously reported that Kv1.4, Kv4.2, and Kv4.3 mRNAs are present in adult and neonatal rat ventricular myocytes, and that transient outward potassium current (Ito) recovers from inactivation with a slow (Ito,s) and a fast (Ito,f) time course. This study was designed to determine the molecular correlates of Ito,s and Ito,f in cultured neonatal rat ventricular myocytes (NRVM) employing dominant-negative adenoviral infections to manipulate the function of endogenous Ito-encoding K+ channels. Western blot data from cultured NRVM showed that Kv1.4, Kv4.2, and Kv4.3 channel proteins are present in these myocytes. The biphasic recovery from inactivation of Ito in control GFP-infected myocytes demonstrated equal contribution of Ito,s and Ito,f in NRVM. Infection of cultured NRVM with adenoviruses expressing full-length Kv1.4 or Kv4.2 genes generated currents with recovery from inactivation kinetics similar to native Ito,s and Ito,f in GFP-infected myocytes, respectively. Overexpression of dominant-negative truncated Kv1.4 transgene (Kv1.4N) caused a 51% reduction in Ito, selectively removing the slowly recovering Ito,s. Overexpression of dominant-negative Kv4.2N reduced Ito by 53% and eliminated the fast-recovering Ito,f. Our results establish that, in neonatal rat ventricular myocytes, the shaker Kv1 family (probably Kv1.4 and/or Kv1.7) underlies Ito,s, and that the shal Kv4 family (probably Kv4.2 and Kv4.3) is responsible for Ito,f.
AB - We have previously reported that Kv1.4, Kv4.2, and Kv4.3 mRNAs are present in adult and neonatal rat ventricular myocytes, and that transient outward potassium current (Ito) recovers from inactivation with a slow (Ito,s) and a fast (Ito,f) time course. This study was designed to determine the molecular correlates of Ito,s and Ito,f in cultured neonatal rat ventricular myocytes (NRVM) employing dominant-negative adenoviral infections to manipulate the function of endogenous Ito-encoding K+ channels. Western blot data from cultured NRVM showed that Kv1.4, Kv4.2, and Kv4.3 channel proteins are present in these myocytes. The biphasic recovery from inactivation of Ito in control GFP-infected myocytes demonstrated equal contribution of Ito,s and Ito,f in NRVM. Infection of cultured NRVM with adenoviruses expressing full-length Kv1.4 or Kv4.2 genes generated currents with recovery from inactivation kinetics similar to native Ito,s and Ito,f in GFP-infected myocytes, respectively. Overexpression of dominant-negative truncated Kv1.4 transgene (Kv1.4N) caused a 51% reduction in Ito, selectively removing the slowly recovering Ito,s. Overexpression of dominant-negative Kv4.2N reduced Ito by 53% and eliminated the fast-recovering Ito,f. Our results establish that, in neonatal rat ventricular myocytes, the shaker Kv1 family (probably Kv1.4 and/or Kv1.7) underlies Ito,s, and that the shal Kv4 family (probably Kv4.2 and Kv4.3) is responsible for Ito,f.
KW - Kv1.4
KW - Kv4.2
KW - Neonatal myocytes
KW - Transient outward K current
UR - http://www.scopus.com/inward/record.url?scp=0035997220&partnerID=8YFLogxK
U2 - 10.1007/s00109-002-0325-7
DO - 10.1007/s00109-002-0325-7
M3 - Article
C2 - 12072910
AN - SCOPUS:0035997220
SN - 0946-2716
VL - 80
SP - 351
EP - 358
JO - Journal of Molecular Medicine
JF - Journal of Molecular Medicine
IS - 6
ER -