Voltage-independent changes in L-type Ca(2+) current uncoupled from SR Ca(2+) release in cardiac myocytes
| Autor: | Edward G. Lakatta, Andrzej M. Janczewski, Michael D. Stern |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Calcium Channels
L-Type Physiology Heart Ventricles Sarcoplasm Physiology (medical) Myocyte Animals Pyrroles Egtazic Acid Chelating Agents Chemistry Myocardium Ca2 current Electric Conductivity Anatomy Rats Electrophysiology Cytosol Calcium Channel Agonists Sarcoplasmic Reticulum Reticular connective tissue Biophysics Calcium Ca2 release Current (fluid) Cardiology and Cardiovascular Medicine Voltage |
| Zdroj: | Europe PubMed Central |
| ISSN: | 0363-6135 |
| Popis: | To determine the effect of voltage-independent alterations of L-type Ca2+ current ( I Ca) on the sarcoplasmic reticular (SR) Ca2+ release in cardiac myocytes, we measured I Ca and cytosolic Ca2+ transients (Cai 2+; intracellular Ca2+ concentration) in voltage-clamped rat ventricular myocytes during 1) an abrupt increase of extracellular [Ca2+] (Cao 2+) or 2) application of 1 μM FPL-64176, a Ca2+channel agonist, to selectively alter I Ca in the absence of changes in SR Ca2+ loading. On the first depolarization in higher Cao 2+, peak I Ca was increased by 46 ± 6% ( P < 0.001), but the increases in the maximal rate of rise of Cai 2+(dCai 2+/d t max, where t is time; an index of SR Ca2+ release flux) and the Cai 2+ transient amplitude were not significant. Rapid exposure to FPL-64176 greatly slowed inactivation of I Ca, increasing its time integral by 117 ± 8% ( P < 0.001) without significantly increasing peak I Ca, dCai 2+/d t max, or amplitude of the corresponding Cai 2+ transient. Prolongation of exposure to higher Cao 2+ or FPL-64176 did not further increase peak I Ca but greatly increased dCai 2+/d t max, Cai 2+ transient amplitude, and the gain of Ca2+ release (dCai 2+/d t max/ I Ca), evidently due to augmentation of the SR Ca2+ loading. Also, the time to peak dCai 2+/d t maxwas significantly increased in the continuous presence of higher Cao 2+ (by 37 ± 5%, P < 0.001) or FPL-64176 (by 63 ± 5%, P < 0.002). Our experiments provide the first evidence of a marked disparity between an increased peak I Ca and the corresponding SR Ca2+ release. We attribute this to saturation of the SR Ca2+ release flux as predicted by local control theory. Prolongation of the SR Ca2+ release flux, caused by combined actions of a larger I Ca and maximally augmented SR Ca2+ loading, might reflect additional Ca2+ release from corbular SR. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|