Mitochondria regulate inactivation of L-type Ca2+ channels in rat heart

Citation
Ja. Sanchez et al., Mitochondria regulate inactivation of L-type Ca2+ channels in rat heart, J PHYSL LON, 536(2), 2001, pp. 387-396
Citations number
47
Categorie Soggetti
Physiology
Journal title
JOURNAL OF PHYSIOLOGY-LONDON
ISSN journal
00223751 → ACNP
Volume
536
Issue
2
Year of publication
2001
Pages
387 - 396
Database
ISI
SICI code
0022-3751(20011015)536:2<387:MRIOLC>2.0.ZU;2-#
Abstract
1. L-type Ca2+ channels play an important role in vital cell functions such as muscle contraction and hormone secretion. Both a voltage-dependent and a Ca2+-dependent process inactivate these channels. Here we present evidenc e that inhibition of the mitochondrial Ca2+ import mechanism in rat (Spragu e-Dawley) ventricular myocytes by ruthenium red (RR), by RON or by carbonyl cyanide m-chlorophenylhydrazone (CCCP) decreases the magnitude of electric ally evoked transient elevations of cytosolic Ca2+ concentration ([Ca2+](c) ). These agents were most effective at stimulus rates greater than 1 Hz. 2. RR and CCCP also caused a significant delay in the recovery from inactiv ation of L-type Ca2+ currents (I-Ca). This suggests that sequestration of c ytosolic Ca2+, probably near the, mouth of L-type Ca2+ channels, into mitoc hondria. during cardiac contractile cycles, helps to remove the Ca2+-depend ent inactivation of L-type Ca2+ channels. 3. We conclude that impairment of mitochondrial Ca2+ transport has no impac t on either L-type Ca2+ currents or SR Ca2+ release at low stimulation freq uencies (e.g. 0.1 Hz); however, it causes a depression of cytosolic: Ca2+ t ransients attributable to an impaired recovery of L-type Ca2+ currents from inactivation at high stimulation frequencies (e.g. 3 Hz). The impairment o f mitochondrial Ca2+ uptake and subsequent effects on Ca2+ transients at hi gh frequencies at room temperature could be physiologically relevant since the normal heart rate of rat is around 5 Hz at body temperature. The role o f mitochondria in clearing Ca2+ in the micro-domain near L-type Ca2+ channe ls could be impaired during high frequencies of heart beats such as in vent ricular tachycardia, explaining, at least in part, the reduction of muscle contractility.