Exercise Training Upregulates SK+ Channel Function in the Hypothalamic Paraventricular Nucleus (PVN) of Animals

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Department of Kinesiology and Integrative Physiology


Increased sympathetic outflow is a hallmark of cardiovascular disease (CVD). Previously, our lab demonstrated that small conductance Ca2+ activated K channels (SK+) expressed in the PVN play a crucial role in regulating sympathetic outflow, and SK+ currents were significantly decreased in rats with salt-sensitive hypertension (SSH). Since SK+ channels among autonomic PVN neurons play a crucial role in regulating sympathetic outflow in SSH, antihypertensive therapies targeted at upregulating SK+ channel expression in the PVN should be pursued. Exercise is a powerful, non-pharmacological intervention to treat CVD, however, the interaction between SK+ channels among the hypothalamic PVN and exercise is unknown. The objective is to determine the role of exercise in regulating SK+ channels function and sympathetic outflow as well as arterial blood pressure (ABP) in animals. We hypothesize that exercise upregulates SK+ channel function in the PVN and attenuates sympathetic outflow. To test this hypothesis, Sprague Dawley (SD) rats are divided into sedentary (SED) and exercise (EXT) groups based on their willingness to run on a motorized treadmill. Exercise intensity is determined through a maximum exercise capacity test and rats run at 70% of their exercise capacity speed for 30 minutes 5 days/week for 8-10 weeks. Then rats are anesthetized and renal sympathetic nerve activity (RSNA) and ABP are recorded following bilateral PVN injections of apamin, a selective SK+ channel blocker (0.25mM, 60nL/side). We found that the RSNA response to PVN apamin trended toward significance in EXT rats compared with SED rats (342.1 ± 164.2 % baseline, n=6 vs 120.9 ± 25.1 % baseline, n=3; p = 0.0598). The corresponding ABP response to apamin was not significantly different in EXT rats compared with SED rats (16.5 ± 5.7 mmHg, n=6 vs 24.6 ± 7.2, n=3; p = 0.1039). Collectively, these results indicate exercise activates PVN SK+ channels function and reduces sympathetic outflow. The improvement of channel function or increase in expression may contribute to the beneficial effects of exercise on reducing sympathetic outflow in patients with CVD, including hypertension.

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FASEB journal : official publication of the Federation of American Societies for Experimental Biology