1. Role of Ion Channels in Human Physiology Kim, Sung Joon Department of Physiology, Department of Biomedical Sciences Seoul National University College of Medicine 13:30-14:30, March 16, Friday, 2012 Room 103, Building 1, DGIST Abstract 1)Aims: A moderate increase in extracellular [K + ] ([K + ] e ) induces relaxation of small arteries via activating inwardly rectifying K + current (I Kir ). The K + -vasodilation is an important mechanism for exercise-induced hyperemia in skeletal muscle. We investigated whether I Kir and K + -vasodilation are enhanced in deep femoral arteries (DFA) from exercise-trained rats (ET-rats, treadmill-running: 20 min at 20 m/min, six days for two weeks). The effects of ET on K + -vasodilation and I Kir were also investigated in cerebral (CA) and mesenteric arteries. Methods and Results: The K + -vasodilation of DFA and the density of I Kir and voltage-gated K + current (I Kv ) were increased in DFA myocytes of ET-rats. The myogenic tone of DFA was unchanged by exercise. Although similar functional up-regulations of I Kir and I Kv were observed in CA myocytes, the K + -vasodilation was not increased in CA of ET-rats. Interestingly, concomitant to the increases in I Kir and I Kv, background Na + conductance was also increased in the CA myocytes. However, such an effect was not observed in DFA myocytes from ET-rats. Neither I Kir nor K + -vasodilation was observed in mesenteric arteries of ET-rats. Conclusion: The present study provides evidence to report that regular exercise up-regulates I Kir in DFA and CA myocytes. Although the increase in I Kir was similarly observed in two types of arteries, augmentation of K + - relaxation was observed only in DFA of ET-rats, possibly due to the increased Na + conductance in CA myocytes. The increases in I Kir and K + -vasodilation of the arteries of skeletal muscle suggest novel mechanisms of improved exercise hyperemia with physical training. 2)Role of thromboxane A2- activated nonselective cation channels in hypoxic pulmonary vasoconstriction of rat. Am J Physiol Cell Physiol 302: C307–C317, 2012. First published October 12, 2011; doi:10.1152/ajpcell.00153.2011.— Hypoxia-induced pulmonary vasoconstriction (HPV) is critical for matching of ventilation/perfusion in lungs. Although hypoxic inhibition of K channels has been a leading hypothesis for depolarization of pulmonary arterial smooth muscle cells (PASMCs) under hypoxia, pharmacological inhibition of K channels does not induce significant contraction in rat pulmonary arteries. Because a partial contraction by thromboxane A2 (TXA2) is required for induction of HPV, we hypothesize that TXA2 receptor (TP) stimulation might activate depolarizing nonselective cation channels (NSCs). Consistently, we found that 5–10 nM U46619, a stable agonist for TP, was indispensible for contraction of rat pulmonary arteries by 4-aminopyridine, a blocker of voltage-gated K channel (Kv). Whole cell voltage clamp with rat PASMC revealed that U46619 induced a NSC current (INSC,TXA2) with weakly outward rectifying current- voltage relation. INSC,TXA2 was blocked by ruthenium red (RR), an antagonist of the transient receptor potential vanilloid-related channel (TRPV) subfamily. 2-Aminoethoxydiphenyl borate, an agonist for TRPV1–3, consistently activated NSC channels in PASMCs. In contrast, agonists for TRPV1 (capsaicin), TRPV3 (camphor), or TRPV4 (-PDD) rarely induced an increase in the membrane conductance of PASMCs. RT-PCR analysis showed the expression of transcripts for TRPV2 and -4 in rat PASMCs. Finally, it was confirmed that pretreatment with RR largely inhibited HPV in the presence of U46619. The pretreatment with agonists for TRPV1 (capsaicin) and TRPV4 (-PDD) was ineffective as pretone agents for HPV. Taken together, it is suggested that the concerted effects of INSC,TXA2 activation and Kv inhibition under hypoxia induce membrane depolarization sufficient for HPV. TRPV2 is carefully suggested as the TXA2-activated NSC in rat PASMC. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Person in charge : Jeong Min Lee Contact: yjm0329@dgist.ac.kr, 053)785-6101yjm0329@dgist.ac.kr