Affiliation:
1. From the Departments of Pharmacology (M.V.B., M.J.M., D.L.C., H.C.S.) and Medicine (S.L., H.C.S.), Duke University Medical Center, and the Department of Biomedical Engineering (R.L.R.), School of Engineering, Duke University, Durham, NC.
Abstract
Abstract
The molecular basis of K
+
currents that generate repolarization in the heart is uncertain. In part, this reflects the similar functional properties different K
+
channel clones display when heterologously expressed, in addition to the molecular diversity of the voltage-gated K
+
channel family. To determine the identity, regional distribution, and cellular distribution of voltage-sensitive K
+
channel mRNA subunits expressed in ferret heart, we used fluorescent labeled oligonucleotide probes to perform in situ hybridization studies on enzymatically isolated myocytes from the sinoatrial (SA) node, right and left atria, right and left ventricles, and interatrial and interventricular septa. The most widely distributed K
+
channel transcripts in the ferret heart were Kv1.5 (present in 69.3% to 85.6% of myocytes tested, depending on the anatomic region from which myocytes were isolated) and Kv1.4 (46.1% to 93.7%), followed by Kv1.2, Kv2.1, and Kv4.2. Surprisingly, many myocytes contain transcripts for Kv1.3, Kv2.2, Kv4.1, Kv5.1, and members of the Kv3 family. Kv1.1, Kv1.6, and Kv6.1, which were rarely expressed in working myocytes, were more commonly expressed in SA nodal cells. IRK was expressed in ventricular (84.3% to 92.8%) and atrial (52.4% to 64.0%) cells but was nearly absent (6.6%) in SA nodal cells; minK was most frequently expressed in SA nodal cells (33.7%) as opposed to working myocytes (10.3% to 29.3%). Two gene products implicated in long-QT syndrome,
ERG
and KvLQT1, were common in all anatomic regions (41.1% to 58.2% and 52.1% to 71.8%, respectively). These results show that the diversity of K
+
channel mRNA in heart is greater than previously suspected and that the molecular basis of K
+
channels may vary from cell to cell within distinct regions of the heart and also between major anatomic regions.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine,Physiology
Reference69 articles.
1. Schuessler RB Boineau JP Bromberg BI Hand DE Yamauchi S Cox JL. Normal and abnormal activation of the atrium. In: Zipes DP Jalife J eds. Cardiac Electrophysiology: From Cell to Bedside. 2nd ed. Philadelphia Pa: WB Saunders Co; 1995:543-562.
2. Allessie MA. Reentrant mechanisms underlying atrial fibrillation. In: Zipes DP Jalife J eds. Cardiac Electrophysiology: From Cell to Bedside. 2nd ed. Philadelphia Pa: WB Saunders Co; 1995:562-566.
3. Jackman WM Nakagawa H Heidbüchel H Beckman K McClelland J Lazzara R. Three forms of atrioventricular nodal (junctional) reentrant tachycardia: differential diagnosis electrophysiological characteristics and implications for anatomy of the reentrant circuit. In: Zipes DP Jalife J eds. Cardiac Electrophysiology: From Cell to Bedside. 2nd ed. Philadelphia Pa: WB Saunders Co; 1995:620-637.
4. Waldo AL. Atrial flutter: mechanisms clinical features and management. In: Zipes DP Jalife J eds. Cardiac Electrophysiology: From Cell to Bedside. 2nd ed. Philadelphia Pa: WB Saunders Co; 1995:666-681.
5. Anumonwo JMB Jalife J. Cellular and subcellular mechanisms of pacemaker activity initiation and synchronization in the heart. In: Zipes DP Jalife J eds. Cardiac Electrophysiology: From Cell to Bedside. 2nd ed. Philadelphia Pa: WB Saunders Co; 1995:151-163.
Cited by
95 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献