| Project/Area Number |
10559002
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B).
|
| Allocation Type | Single-year Grants |
|---|
| Section | 展開研究 |
|---|
| Research Field |
広領域
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
YANAGISAWA Teruyuki Sch.Med., Dept.Pharmacol., Tohoku University, Professor, 大学院・医学系研究科, 教授 (90133941)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MURAKAMI Manabu Sch.Med., Dept.Pharmacol., Tohoku University, Res. Associate, 大学院・医学系研究科, 助手 (80302090)
SUKEGAWA Jun Sch.Med., Dept.Pharmacol., Tohoku University, Lecturer, 大学院・医学系研究科, 講師 (30187687)
NUNOKI Kazuo Sch.Med., Dept.Pharmacol., Tohoku University, Lecturer, 大学院・医学系研究科, 講師 (10172743)
MATSUE Tomokazu Sch.Eng., Dept.Biomol., Tohoku University, Professor, 大学院・工学研究科, 教授 (70173797)
KOBAYASHI Nagao Sch.Sci., Dept.Chem., Tohoku University, Professor, 大学院・理学研究科, 教授 (60124575)
|
|---|
| Project Period (FY) |
1998 – 2000
|
| Keywords | K^+ channels / Ca^<2+> chanels / Inactivation / Adaptation / Knockout mouse / Dihydropyridine / Salt-sensitive hypertension |
|---|
| Research Abstract |
N-type inactivation of rat Kv1.4 channels with one, two, or four inactivation balls was investigated using homogeneous populations of channels expressed in Xenopus oocytes. Tandem dimeric and tetrameric constructs of Kv1.4 were made. Channels encoded by tandem cDNAs Kv1.4-Kv1.4Delta1-145 and Kv1.4-[Kv1.4Delta1-145] (3) have two or only one tethered inactivation ball, respectively, whereas Kv1.4 itself encodes channels having four inactivation balls. The time constants for inactivation of macroscopic currents were increased significantly as the number of inactivation balls was decreased, whereas the time constants for recovery from inactivation were not modified. The ratios of the rate constants of inactivation (k (inact) ) of Kv1.4-Kv1.4Delta1-145 and Kv1.4-[Kv1.4Delta1-145] (3) channels to that of the Kv1.4 channel were 0.65 and 0.4, respectively, whereas the ratios of the rate constant of recovery (k (rec) ) of these channels to that of Kv1.4 were almost unity. The rate constants k (
… More
inact) for channels having two and four inactivation balls are smaller than those that would be expected if inactivation balls on each channel are independent, suggesting some interaction occurs between inactivation balls. Furthermore, noninactivating current became apparent as the number of inactivation balls on a channel was decreased.
Voltage-dependent calcium channels are crucially important for calcitum influx and following smooth muscle contraction. Beta subunits of these channels are known to modify calcium currerns through pore-forming alfa1 subunits. Among four reported independent beta subunit, the beta3 subunit in cardiovascular system, we have analyzed beta3-null mice. Electrophysiological examinations proved the existence of dihydropyridine (DHP)-sensitive, L-type calcium channels in the smooth muscle cell. Beta3-null mice show no apparent changes in smooth muscle contraction and sensitivity to DHP, and normal blood pressure when they are raised on a normal diet, but the beta3 subunit deficient mice show elevated blood pressure in response to a high-salt diet, with significant reductions in plasma catecholamine concentration. Our finding strongly suggests the adaptation to the null mutation of calcium channel beta subunit results in salt-sensitive hypertension. Less
|
