[Observation of functional remodeling of Ca2+-activated Cl- channel in pacing-induced canine failing heart].
OBJECTIVE
To study whether Ca(2+)-activated Cl(-) current (I(to2)) contributes to the functional remodeling of the failing heart.


METHODS
The cardiac myocytes were isolated enzymatically from rapidly pacing-induced failing canine hearts (HF) at room temperature. Patch-Clamp whole cell recording technique was employed to record the I(to2). The Cl(-) transport blocker 4, 4'-diisothiocyanostilbene-2, 2'-disulfonic acid (DIDS, 200 micromol) was used to isolated the I(to2). The relations of I(to2) to L-type Ca(2+) current (I(Ca-L)) and to the membrane voltage under the constant intracellular [Ca(2+)]i were evaluated in HF and the normal hearts.


RESULTS
We found that the current density of I(to2) was significantly decreased in HF cells compared with the controls. At membrane voltage of 20 mV, for example, the I(to2) density was (3.02 +/- 0.54) pA/pF in control cells (n = 7) vs. (1.31 +/- 0.25) pA/pF in HF (n = 8) cells, P < 0.05. While the averaged I(Ca-L) density did not show difference between two groups. The time constant of current decay of I(to2) was similar in both types of cells. However, in intracellular Ca(2+) clamped mode with 100 micromol [Ca(2+)]i, I(to2) density was increased significantly in HF cells at membrane voltage of +30 mV or higher.


CONCLUSIONS
Our results suggest that the decrease of I(to2) density may contribute to the prolongation of the action potential in failing heart. I(to2) density abnormality may cause cardiac arrhythmia and a delayed after-depolarization. Impaired Ca(2+) handing in HF cells rather than reduced CLCA function itself may result in this abnormality.
Pu
Jie-lin
JL
Center for Cardiac Arrhythmia, Fu Wai Cardiovascular Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100037, China.
Li
Ning
N
Ma
Ke-juan
KJ
Wang
Hong-tao
HT
Teng
Si-yong
SY
Makielski
Jonathon C
JC
D000818:Animals; D002118:Calcium / Q000502:physiology*; D020746:Calcium Channels, L-Type / Q000502:physiology; D018118:Chloride Channels / Q000502:physiology*; D004285:Dogs; D006333:Heart Failure / Q000503:physiopathology*; D018408:Patch-Clamp Techniques; D020257:Ventricular Remodeling / Q000502:physiology*
D020746:Calcium Channels, L-Type; D018118:Chloride Channels; D002118:Calcium