A new, sympathetic look at KATP channels in the heart

See article by Oe et al. ([10], pages 125–134) in this issue. Myocardial ATP-sensitive potassium (KATP) channels are closed during physiological conditions but are activated by a decrease in intracellular ATP-concentration [1]. KATP activation during myocardial ischaemia postpones the onset of irreversible damage, and reduces the size of the area of myocardial infarction (reviewed in [2]). Blockade of KATP channels by sulfonylurea derivatives and sodium 5-hydroxydecanoate (5-HD) reverses these cardioprotective effects [2]. The exact mechanism of cardioprotection by KATP activation has not yet been unravelled. Shortening of action potential duration due to the opening of KATP channels [4,5], the previously supposed underlying mechanism, is not a prerequisite for cardioprotection to occur [3]. Mitochondrial KATP channels may play a role, but further studies are needed for clarification [6]. Another potential contributing mechanism involves KATP channels in cardiac sympathetic nerve-endings. Throughout the central nervous system, KATP channels are located on both pre- and postsynaptic neurones [7]. Release of neurotransmitters in the brain can be influenced by neuronal KATP modulation, both under normoxic and ischaemic-like conditions [8,9]. In this edition of Cardiovascular Research, Oe et al. show a relationship between KATP modulation and norepinephrine release from the atrium under physiological conditions [10]. To correctly interpret their results and appreciate the potential role of KATP channels in catecholamine release modulation during myocardial ischaemia, understanding of the mechanisms of catecholamine secretion during physiological and pathophysiological conditions is essential. In the sympathetic nerve terminals, norepinephrine (NE) is contained … * Corresponding author. Tel.: +31-20-566-3265; fax: +31-20-697-5458 c.a.remme{at}amc.uva.nl