Figure 7.
Effects of AMPK activation and inhibition on ouabain-induced SD. a, AMPK inhibition resulted in a 70% decrease in the number of preparations having at least one ouabain-induced SD-like event. b, Time to onset of ouabain-induced SD-like events was significantly decreased by AMPK activation and significantly increased by AMPK inhibition. Significant treatment effects were found (one-way ANOVA, p < 0.001; control and AICAR, N = 10; compound-C, N = 3). c, AMPK activation also increased the number of SD-like events compared to control preparations and those treated with 10−4 m compound-C (cmpd-C), and significant effects of treatment were found (one-way ANOVA, p = 0.001; control and AICAR, N = 10; compound-C, N = 3). Control preparations and those treated with compound-C were not significantly different, likely because of the small sample size as a result of the low proportion of preparations treated with compound-C that had at least one SD-like event. d, AMPK activation significantly increased the duration of the initial ouabain-induced SD-like event, whereas AMPK inhibition significantly decreased SD-like event duration (one-way ANOVA, p = 0.001; control and AICAR, N = 10; compound-C, N = 3). e, Overlay of individual [K+]o surges induced by ouabain in a control preparation (Fig. 5a), a preparation treated with AICAR (Fig. 5b), and a preparation treated with compound-C (Fig. 6a) to illustrate that on average AICAR decreases both phases (“Top” slope and “Down” slope) of the rate of [K+]o clearance, whereas compound-C has a tendency to increase rates of [K+]o clearance (see Results for means and SE). Traces were scaled to 100% amplitude from baseline to the peak [K+]o to aid comparison. Letters in histogram bars represent statistical groupings, whereby bars with different letters are significantly different using a post hoc Tukey test (p < 0.05). Error bars represent SEM.