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- Title
Cross-talk between ß<sub>1</sub>-adrenoceptors and ET<sub>A</sub> receptors in modulation of the slow component of delayed rectifier K<sup>+</sup> currents.
- Authors
Lin, Changqing; Nagai, Mirei; Ishigaki, Daisuke; Hayasaka, Kiyoshi; Endoh, Masao; Ishii, Kuniaki
- Abstract
Delayed rectifier K+ currents (IK) play a critical role in determining cardiac action potential duration (APD). Modulation ofIK affects cardiac excitability critically. There are three components of cardiac delayed rectifier, and the slowly activating component (IKs) is influenced strongly by a variety of stimuli. Plasma levels of noradrenaline and endothelin are elevated in heart failure, and arrhythmias are promoted by such humoral abnormalities through modulation of ion channels. It has been reported that protein kinase A (PKA) and protein kinase C (PKC) modulateIKs from human minK in a complex manner. In the present study, we coexpressed human minK with the human ß1-adrenoceptor (hß1AR) and the endothelin receptor subtype A (hETAR) inXenopusoocytes and investigated the effects of receptor activation on the currents (IKs) flowing through the oocytes. ET-1 modulatedIKs biphasically: a transient increase followed by a decrease. The PKC inhibitor chelerythrine completely inhibited the effects of ET-1. Intracellular EGTA abolished the transient increase by ET-1 and partially inhibited the subsequent decrease in the currents. WhenIKs was increased by 10-6 M isoproterenol (ISO), ET-1 did not increase but rather decreased the current to an even greater extent than under control conditions. In addition, the effects of ISO onIKs were suppressed by ETAR stimulation. These data indicate thatIKs can be regulated by cross-talk between the ETAR and ß1AR systems in addition to direct regulation by each receptor system.
- Subjects
ADRENERGIC receptors; HEART failure; HEART beat; CARDIOVASCULAR agents; MEMBRANE proteins; ARRHYTHMIA
- Publication
Naunyn-Schmiedeberg's Archives of Pharmacology, 2005, Vol 371, Issue 2, p133
- ISSN
0028-1298
- Publication type
Article
- DOI
10.1007/s00210-005-1018-x