J Physiol Society Meetings
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Physiol Volume 586, Number 11, 2767-2778, June 1, 2008 DOI: 10.1113/jphysiol.2007.148932
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
586/11/2767    most recent
jphysiol.2007.148932v1
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fukuzaki, K.
Right arrow Articles by Nakaya, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fukuzaki, K.
Right arrow Articles by Nakaya, H.
Related Collections
Right arrow Cardiovascular

CARDIOVASCULAR

Role of sarcolemmal ATP-sensitive K+ channels in the regulation of sinoatrial node automaticity: an evaluation using Kir6.2-deficient mice

 Koichi Fukuzaki1, Toshiaki Sato1, Takashi Miki2, Susumu Seino3 and Haruaki Nakaya1

1 Department of Pharmacology
2 Department of Autonomic Physiology, Chiba University Graduate School of Medicine, Chiba, Japan
3 Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan

The role of cardiac sarcolemmal ATP-sensitive K+ (KATP) channels in the regulation of sinoatrial node (SAN) automaticity is not well defined. Using mice with homozygous knockout (KO) of the Kir6.2 (a pore-forming subunit of cardiac KATP channel) gene, we investigated the pathophysiological role of KATP channels in SAN cells during hypoxia. Langendorff-perfused mouse hearts were exposed to hypoxic and glucose-free conditions (hypoxia). After 5 min of hypoxia, sinus cycle length (CL) was prolonged from 207 ± 10 to 613 ± 84 ms (P < 0.001) in wild-type (WT) hearts. In Kir6.2 KO hearts, CL was slightly prolonged from 198 ± 17 to 265 ± 32 ms. The CL of spontaneous action potentials of WT SAN cells, recorded in the current-clamp mode, was markedly prolonged from 410 ± 56 to 605 ± 108 ms (n = 6, P < 0.05) with a decrease of the slope of the diastolic depolarization (SDD) after the application of the K+ channel opener pinacidil (100 µM). Pinacidil induced a glibenclamide (1 µM)-sensitive outward current, which was recorded in the voltage-clamp mode, only in WT SAN cells. During metabolic inhibition by 2,4-dinitrophenol, CL was prolonged from 292 ± 38 to 585 ± 91 ms (P < 0.05) with a decrease of SDD in WT SAN cells but not in Kir6.2 KO SAN cells. Diastolic Ca2+ concentration, measured by fluo-3 fluorescence, was decreased in WT SAN cells but increased in Kir6.2 KO SAN cells after short-term metabolic inhibition. In conclusion, the present study using Kir6.2 KO mice indicates that, during hypoxia, activation of sarcolemmal KATP channels in SAN cells inhibits SAN automaticity, which is important for the protection of SAN cells.

(Received 27 November 2007; accepted after revision 10 April 2008; first published online 17 April 2008)
Corresponding author H. Nakaya: Department of Pharmacology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. Email: nakaya{at}faculty.chiba-u.jp






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2008 The Physiological Society.