1992 Fiscal Year Final Research Report Summary
Dual modulation of Ca channels by intracellular Ca^<2+> concentration
| Project/Area Number |
03670443
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Circulatory organs internal medicine
|
|---|
| Research Institution | Tokyo Medical and Dental University, Medical Research Institute |
|---|
Principal Investigator |
HIRANO Yuji Tokyo Medical & Dental University, Medical Research Institute, Research Associate, 難治疾患研究所, 助手 (00181181)
|
|---|
| Project Period (FY) |
1991 – 1992
|
| Keywords | Ca channel / Intracellular Ca^<2+> / Fura 2 / Patch clamp |
|---|
| Research Abstract |
Activities of L-type Ca channels in muscles and neurons are under feedback controls by intracellular Ca concentrations ([Ca]i), which include both Ca-dependent inactivation and potentiation. Little is known,however, about interrelationships between these two opposite functions and the levels of [Ca]i required. With simultaneous optical monitoring of [Ca]i using fura2, we investigated at the single-channel level how tonic changes in [Ca]i modulate cardiac L-type Ca channels. When cytosolic Ca concentrations of myocytes under K-depolarization is altered through changes in bath Ca concentration, activity of Ca channels is reversibly potentiated as [Ca]i exceeds 2 times the resting level, until it reaches the "inactivation" level shortly below the threshold for contraction. Unitary current amplitudes were constant during these observations. Increased probability for channel opening during Ca-dependent potentiation was associated with 1. increased number of available sweeps, 2. increased Po during open sweeps, and 3. increased appearance of "mode2" behavior. We also found that Ca-dependent potentiation was equipped with short term "memory" which is resistant to transient Ca-induced inactivation. The present study provide analysis of Ca-dependence of Ca channel activity for the first time in direct and quantitative way.
|
