Surface electrocardiogram and action potential in mice lacking urea transporter UT-B.
UT-B is a urea transporter protein expressed in the kidney and in many non-renal tissues including erythrocytes, brain, heart, bladder and the testis. The objective of this study was to determine the phenotype of UT-B deletion in the heart. UT-B expression in the heart was studied in wild-type mice vs UT-B null mice by utilizing RT-PCR and Western blot. A surface electrocardiogram (ECG) recording (lead II) was measured in wild-type mice and UT-B null mice at the ages of 6, 16 and 52 weeks. For the action potential recording, the ventricular myocytes of 16 w mice were isolated and recorded by floating microelectrode method. The sodium current was recorded by the patch clamp technique. RT-PCR and Western blot showed the UT-B expression in the heart of wild-type mice. No UT-B transcript and protein was found in UT-B null mice. The ECG recording showed that the P-R interval was significantly prolonged in UT-B null mice ((43.5 +/- 4.2), (45.5 +/- 6.9) and (43.8 +/- 7.6) ms at ages of 6, 16 and 52 weeks) vs wild-type mice ((38.6 +/- 2.9), (38.7 +/- 5.6) and (38.2 +/- 7.3) ms, P<0.05). The atrial ventricular heart block type II and III only appeared in the aging UT-B null mice (52 w old). The amplitude of action potential and V (max) decreased significantly in UT-B null mice ((92.17 +/- 10.56) and (101.89 +/- 9.54) mV/s) vs those in wild-type mice (vs (110.51 +/- 10.38) and (109.53 +/- 10.64) mV/s, P<0.05). The action potential duration at 50% and 90% (APD(50) and APD(90)) was significantly prolonged in UT-B null mice ((123.83 +/- 11.17) and (195.43 +/- 16.41) ms) vs that in wild-type mice ((108.27 +/- 10.85) and (171.00 +/- 15.53) ms, P<0.05). The maximal sodium current decreased significantly in UT-B null mice (-8.80 +/- 0.92) nA vs that in wild-type mice ((-5.98 +/- 1.07) nA, P<0.05). These results provide the first evidence that UT-B deletion causes progressive heart block in mice.
Meng
Yan
Y
Department of Pathophysiology, School of Basic Medicine, Jilin University, Changchun, 130021, China.
Zhao
Chunyan
C
Zhang
Xuexin
X
Zhao
Huashan
H
Guo
Lirong
L
Lü
Bin
B
Zhao
Xuejian
X
Yang
Baoxue
B
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D004562:Electrocardiography; D006327:Heart Block / Q000235:genetics / Q000503:physiopathology; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014508:Urea / Q000097:blood / Q000378:metabolism
D026901:Membrane Transport Proteins; D012333:RNA, Messenger; C452857:urea transporter B, mouse; D014508:Urea