AIM:To observe the changes of atrial fibrillation susceptibility,and the remodeling of atrial myo-cyte action potential,ultrarapid activation delayed rectifier potassium current(IKur)and transient outward potassium cur-rent(Ito)in elderly mice,and to explore the mechanism of atrial fibrillation from the single cell electrophysiological level.METHODS:The C57BL/6J mice were divided into old group(20 months old)and young group(4 months old).Atrial fi-brillation was induced by esophageal atrial pacing.The atrial myocytes were isolated,and action potential and ion currents were recorded with patch-clamp technique.The associated proteins were detected by Western blot technique.RE-SULTS:(1)Compared with young mice,the total incidence of atrial fibrillation was significantly increased in old mice(20.0%at 4 months old vs 60.0%at 20 months old,P<0.01).(2)The action potential duration of atrial myocytes in aged mice was shortened,and more significantly after stimulation.(3)The density of Ito and IKur in atrial myocytes of aged mice increased significantly,from(12.6±1.4)pA/pF to(21.7±1.1)pA/pF,and from(7.5±1.5)pA/pF to(13.3±2.1)pA/pF,respectively(P<0.01).After stimulation,the current increased more significantly,especially in older atrial cells.Compared with the young mice,the steady-state activation curve of Ito in the atrial myocytes of the aged mice shifted towards the depolarization,suggesting that activation of Ito channels in the aged mice increased at the same voltage stimula-tion.(4)Compared with young group,the expression of KV4.2(generating Ito)and KV1.5(generating IKur)proteins in the atrial tissue of the mice in old group was significantly increased,and the expression of caveolin-3 and end-binding protein 1(EB1)was up-regulated,suggesting that the increases in KV4.2 and KV1.5 total channel proteins and effective proteins in the cell membrane might contribute to the increase in the remodeling of potassium currents in the elderly atrial myo-cytes.CONCLUSION:The incidence of atrial fibrillation in elderly mice is significantly augmented,which may be related to the increases in Ito and IKur in atrial myocytes.The remodeling of potassium currents in elderly atrial myocytes is one of the electrophysiological bases leading to the shortening of action potential duration and the occurrence of atrial fibrillation.

AIM:To observe the changes of atrial fibrillation susceptibility,and the remodeling of atrial myo-cyte action potential,ultrarapid activation delayed rectifier potassium current(IKur)and transient outward potassium cur-rent(Ito)in elderly mice,and to explore the mechanism of atrial fibrillation from the single cell electrophysiological level.METHODS:The C57BL/6J mice were divided into old group(20 months old)and young group(4 months old).Atrial fi-brillation was induced by esophageal atrial pacing.The atrial myocytes were isolated,and action potential and ion currents were recorded with patch-clamp technique.The associated proteins were detected by Western blot technique.RE-SULTS:(1)Compared with young mice,the total incidence of atrial fibrillation was significantly increased in old mice(20.0%at 4 months old vs 60.0%at 20 months old,P<0.01).(2)The action potential duration of atrial myocytes in aged mice was shortened,and more significantly after stimulation.(3)The density of Ito and IKur in atrial myocytes of aged mice increased significantly,from(12.6±1.4)pA/pF to(21.7±1.1)pA/pF,and from(7.5±1.5)pA/pF to(13.3±2.1)pA/pF,respectively(P<0.01).After stimulation,the current increased more significantly,especially in older atrial cells.Compared with the young mice,the steady-state activation curve of Ito in the atrial myocytes of the aged mice shifted towards the depolarization,suggesting that activation of Ito channels in the aged mice increased at the same voltage stimula-tion.(4)Compared with young group,the expression of KV4.2(generating Ito)and KV1.5(generating IKur)proteins in the atrial tissue of the mice in old group was significantly increased,and the expression of caveolin-3 and end-binding protein 1(EB1)was up-regulated,suggesting that the increases in KV4.2 and KV1.5 total channel proteins and effective proteins in the cell membrane might contribute to the increase in the remodeling of potassium currents in the elderly atrial myo-cytes.CONCLUSION:The incidence of atrial fibrillation in elderly mice is significantly augmented,which may be related to the increases in Ito and IKur in atrial myocytes.The remodeling of potassium currents in elderly atrial myocytes is one of the electrophysiological bases leading to the shortening of action potential duration and the occurrence of atrial fibrillation.

Objective To observe the variations of thyroid hormone receptors(RTs) mRNA experession during the human brain devlopment. Methods We investigated the ontogeny of TR isoforms in the first and second trimester human fetal different brain areas by semi-quantitative reverse transcriptase-polymerase chain reaction analysis. When we amplified the TR? 2 by PCR, the other sequence was amplified at the same time, it is about 100pb less than the RT? 2, so we cloned it into pGEM-T easy vector to determine its sequence. Results In the first and second trimester human fatal brain, RTs mRNAs were detected in cerebrum, cerebellum, brain, stem, hippocampus, spinal cord, thalamus. TRs mRNAs were relatively higher in cerebrum, cerebellum, hippocampus. In the first trimester human fatal brain, the TR? isoforms mRNAs were higher than TR? 1, In the second trimester human fatal brain, the TR? 2 and TR? 1 were higher than TR? 1. An additional truncated species was detected with the TR? 2 primer set. We submitted its sequencing results to Genbank, comparing it with TR? 2 by BLAST software, the results showed that it is identical to TR? 2 with the exception that it is missing 42 amino acids at 371-412 of TR? 2 sequence, so it is the human TR? 3. At the same time we acquired the Genbank accession number AF522368. Conclusion The spatial and temporal expressions of TR isoforms mRNAs exist in CNS development. We firstly assure the different sequence between human TR?2 and TR?3.