Guest blog: Collaborator Jasna Marinovic, Assistant professor at University of Split School of Medicine
Department of Integrative Physiology
Membrane potential is one of the most basic properties of all living cells that is vital for proper cellular function and homeostasis. At rest, most cells in our body exhibit negative membrane potential, which is primarily established via continuous efflux of potassium (K+) ions through their respective channels. In excitable cells, such as cardiac myocytes, K+-channel opening affects cellular excitability, action potential frequency and duration, with resulting impact on contraction strength, ionic balance, oxygen demand, etc.
Among different subtypes of channels specialized for conducting potassium, a unique group, which is expressed at high density in membrane of cardiac cells, are the ATP-sensitive K+ (KATP) channels. Although under no-stress conditions they do not actively participate in action potential formation, their evolutionary conservation and abundance implicate their physiological importance. Indeed, the KATP channels serve as cellular metabolic sensors, opening in situations of cardiac stress and translating metabolic changes into alterations of membrane potential. Intactness of the KATP channels was shown essential for cardiac tolerance to stress and adaptations to increased workload, such as during increased blood pressure, chronic exercise, oxidative stress, as well as acute damage by cardiac ischemia. In humans, mutations in KATP channel subunits were found in a subset of patients with idiopathic heart failure and were associated with worse clinical outcome as compared to patients without the mutations.
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A recent study performed by joint efforts of scientists from Medical School in Split, Croatia and CERG investigated the role of KATP in exercise-induced beneficial effects in chronic heart failure. The study was performed on rats with surgically-induced massive myocardial infarctions that were followed by the chronic heart failure remodeling. Once again, the beneficial effects of aerobic interval training in failing myocardium were demonstrated, evident by the significantly improved cardiac contractile function in exercised animals. This cardiac functional improvement (such as better Ca2+ handling and tolerance to stress) was associated with up-regulation of KATP channel expression and was significantly reduced by a KATP channel inhibition. This suggests an important role of KATP channels in the cardiac benefits induced by chronic exercise.
In recent published study, researchers examined the effect of aerobic exercise on breast tumors in mice to see if it had a direct effect on the tumor itself. The reason for this is that tumors can become resistant to traditional treatment because of impaired or restricted blood flow. This is problematic since the blood is our transportation system. To put it another way, then blood vessels can be considered railroad tracks in this context, and when the train (blood) does not arrive to the station to deliver the medicine, the tumor does not receive treatment.
There have been made various attempts to improve circulation around these areas where blood is prohibited. One of the many positive effects of exercise is improved blood flow and function of blood, or transportation if you prefer. This study found that exercise both improved function of the blood vessels around the tumor areas, and led to formation of several new blood vessels. Compared with a control group that also received chemotherapy, but did not exercise, they found a significantly better effect on the tumors. The researchers behind this study are convinced that the big difference in the effectiveness of chemotherapy because the exercise led to better blood circulation around the tumors. For all statisticians out there, exercise led to 60% higher density of blood vessels around tumors. In addition, chemotherapy along with exercise resulted in a 1.5 times higher death of cancer cells compared to the control group (a positive cell death within this context).
ASAfter these promising results, they reiterated the experiment with another drug, but in addition, they had a separate group that ONLY received exercise as treatment. Most effective treatment was the combination of both training and chemotherapy. But an interesting fact here is that they found a positive effect, and no statistical difference between the exercise group and the group that received only drug through chemotherapy.
All in all, this is promising news for cancer patients worldwide. Exercise is already shown to be positive for fitness level, quality of life and reduced fatigue in cancer patients. Now it turns out that exercise also may help improve the cancer itself.
Jasna Marinovic, Assistant professor at University of Split School of Medicine
Department of Integrative Physiology