Changes In Function Of Potassium And Calcium Channels Of Vascular Smooth Muscle Cells Due To Short-and Mid-term Simulated Weightlessness In Rats

Previous findings from our laboratory have demonstrated that simulated weightlessness may result in atrophic changes with depressed vasoconstrictor responsiveness in hindquarter vessels, and hypertrophic changes with enhanced vasoconstrictor responsiveness in cerebral arteries in rats. Although it is well established that these changes may originated from the altered transmural pressure and distribution of blood in different vessels, the mechanisms of this differential adaptation in vascular structure and function remain unclear. The adaptations of vascular function and structure are two physiological processesrelated to each other. The calcium and potassium channels of vascular smooth muscle cells (VSMCs) play pivotal role not only in the regulation of the vasoreactivity, but also in the regulation of the proliferation and apoptosis of VSMCs in pathological conditions such as hypertension and pulmonary hypertension. So we speculated that the changes of the local hemodynamics in vessels of different anatomic regions during simulated weightlessness may also lead to adaptive changes in potassium and calcium channels of VSMCs from different arteries, and these changes may contribute to the differential changes in vasoreactivity in turn. To verify our speculation, we investigated the functions of the voltage-dependent potassium channel (Kv) and large conductance calcium-dependent potassium channel (BKca) of VSMCs isolated from hindquarter arteries and cerebral arteries of rats after short- and mid-term simulated weightlessness and compared with that of control rats, using both pharmacological methods and whole cell patch clamp techniques. In addition, the function of voltage-dependent calcium channel (VDC) of VSMCs from small mesenteric arteries after short- and mid-term simulated weightlessness were also investigated using whole cell patch clamp techniques with Ba2+ as charge carrier. The main findings of the present work are as follows:1. changes of BKCa and Kv functions of VSMCs isolated from hindquarter arteries of simulated weightless ratsThe pharmacological experiments demonstrated that, compared with arteries of the control rats, the femoral arterial rings of 1-wk and 4-wk simulated weightless rats showed a decreased contractile responsiveness to 60 mM KC1; their contractile responsiveness to TEA (BKca blocker) or 4-AP (Kv blocker) showed no significant differences between simulated weightless and control rats; however, the ratio of their contractile responsiveness induced by TEA or 4-AP to their responsiveness induced by 60 mM KC1 increased significantly after 1-wk and 4-wk simulated weightlessness, with the difference between 1-wk and 4-wk groups being insignificant. These results suggested increased BKca and Kvchannel functions of VSMCs isolated from femoral arteries of simulated weightless rats. The whole cell patch clamp currents recording showed that the total potassium current densities, the BKca current densities and the Kv current densities of VSMCs in saphenous arteries increased significantly after 1-wk and 4-wk simulated weightlessness, and the increased percentage of potassium channel current densities were similar between 1-wk and 4-wk simulated weightless rats; the BKca current densities and the KV current densities of VSMCs from small mesenteric arteries also increased significantly after 4-wk simulated weightlessness. Compared with the control rats, the VSMCs from saphenous arteries and mesenteric arteries of simulated weightless rats showed more negative membrane potentials after simulated weightlessness, but no significant changes were found in membrane capacity. These findings also suggested that the changes of potassium channel functions happened at the early stages of simulated weightlessness. These potassium channel changes may lead to the decreased vasoreactivity on one hand, and may prevent the proliferation of VSMCs and enhance the apoptosis of VSMCs on the other hand. 2. changes of BKCa and Kv function of VSMCs isolated from cerebral arteries of simulated...