Cardioprotective effects of KATP channel activation during hypoxia in goldfish Carassius auratus

Abstract

SUMMARY The activation of ATP-sensitive potassium (KATP) ion channels in the heart is thought to exert a cardioprotective effect under low oxygen conditions, possibly enhancing tolerance of environmental hypoxia in aquatic vertebrates. The purpose of this study was to examine the possibility that hypoxia-induced activation of cardiac KATP channels, whether in the sarcolemma (sarcKATP) or mitochondria (mitoKATP),enhances viability in cardiac muscle cells from a species highly tolerant of low oxygen environments, the goldfish Carassius auratus. During moderate hypoxia (6–7 kPa), the activation of sarcKATPchannels was indicated by a reduction in transmembrane action potential duration (APD). This response to hypoxia was mimicked by the NO-donor SNAP(100 μmol l–1) and the stable cGMP analog 8-Br-cGMP, but abolished by glibenclamide or l-NAME, an inhibitor of NO synthesis. The mitoKATP channel opener diazoxide did not affect APD. Isolated ventricular muscle cells were then incubated under normoxic and hypoxic conditions. Cell viability was decreased in hypoxia; however, the negative effects of low oxygen were reduced during simultaneous exposure to SNAP,8-Br-cGMP, and diazoxide. The cardioprotective effect of diazoxide, but not 8-Br-cGMP, was reduced by the mitoKATP channel blocker 5-HD. These data suggest that hypoxia-induced activation of sarcKATP or mitoKATP channels could enhance tolerance of low-oxygen environments in this species, and that sarcKATP activity is increased through a NO and cGMP-dependent pathway.

The ATP-sensitive potassium (K ATP ) channel-encoded dSUR gene is required for Drosophila heart function and is regulated by tinman

“…Our data are consistent, with dSUR in Drosophila providing a similar protective mechanism against hypoxia. Moreover, a recent study in goldfish K ATP channel function (38) revealed that the involvement of K ATP in IPC is widely conserved, including in highly hypoxia-tolerant species.…”

Effects of prolonged anoxia on electrical activity of the heart in Crucian carp (Carassius carassius)

“…Although an ATP-sensitive K + current exists in crucian carp ventricular myocytes, it is not activated under prolonged anoxia Vornanen, 2002, 2003). Conversely, it has been suggested that in the heart of warm-acclimated (+21°C) goldfish (Carassius auratus), an anoxia-tolerant related species, hypoxia causes a slight shortening (15%) of ventricular AP via opening of the ATP-sensitive K + channels (Chen et al, 2005). Whether the difference between crucian carp and goldfish is species specific, related to highly different acclimation and experimental temperatures, or indicates a real difference in their responses to hypoxia versus anoxia, remains to be shown.…”

“…The outward K + current (I K(ATP) ) reduces plateau duration of the cardiac AP, and hence contractility of cardiac myocytes and thus energy usage by the cell. Analogous to mammalian hearts, shortening of the ventricular AP via opening of the ATP-sensitive K + channels has been suggested to protect hypoxic goldfish (Carassius auratus) hearts (Chen et al, 2005;Cameron et al, 2013). However, these observations are based on short-term in vitro studies, while direct demonstration of hypoxic shortening of the QT interval in vivo under prolonged oxygen shortage is lacking.…”

“…We therefore hypothesised that winter-acclimatised crucian carp will elicit a sustained bradycardia in anoxic and cold waters to reduce energy consumption, and that prolongation of the ventricular AP is necessary to maintain a constant diastole/systole duration (DSD) for uninterrupted circulation of blood. If, however, there were no reduction in f H in anoxia (Stecyk et al, 2004), then protection to the heart might be provided by the shortening of the AP duration via increased activity of ATP-sensitive K + channels (Chen et al, 2005). To test these hypotheses, seasonally acclimatised winter fish were exposed to controlled anoxia in the laboratory for several weeks at their natural habitat temperature in winter.…”

In situcardiac function in Atlantic cod (Gadus morhua): effects of acute and chronic hypoxia

“…Amongst these are ATP-sensitive potassium (K ATP ) channels [both sarcolemmal (sK ATP ) and mitochondrial (mK ATP )], nitric oxide (NO), HIF-1a, and various protein kinases (including PKC) (Kolar and Ostadal, 2004;Ostadal and Kolar, 2007). However, research on the importance of these mechanisms in conferring cardioprotection in fishes is still in its infancy, and is often contradictory (see MacCormack and Driedzic, 2002;Chen et al, 2005;Rissanen et al, 2006;Marques et al, 2008).…”