Simulated calcium current can both cause calcium loading in and trigger calcium release from the sarcoplasmic reticulum of a skinned canine cardiac Purkinje cell.

Abstract

Skinned canine cardiac Purkinje cells were stimulated by regularly repeated microinjection-aspiration sequences that were programmed to simulate the fast initial component of the transsarcolemmal Ca from the sarcoplasmic reticulum (SR) . The simulated slow component did not affect the tension transient during which it was first introduced but it potentiated the subsequent transients . The potentiation was not observed when the SR function had been destroyed by detergent. The potentiation decreased progressively when the slow component was separated by an increasing time interval from the fast component. The potentiation was progressive over several beats under conditions that decreased the rate of Ca" accumulation into the SR (deletion of calmodulin from the solutions; a decrease of the temperature from 22 to 12°C). In the presence of a slow component, an increase of frequency caused a positive staircase, and the introduction of an extrasystole caused a postextrasystolic potentiation . There was a negative staircase and no postextrasystolic potentiation in the absence of a slow component. These results can be explained by a time-and Ca 2 '-dependent functional separation of the release and accumulation processes of the SR, rather than by Ca 21 circulation between anatomically distinct loading and release compartments. The fast initial component of transsarcolemmal Ca 21 current would trigger Ca 2' release, whereas the slow component would load the SR with an amount of Ca2' available for release during the subsequent tension transients .

Sarcoplasmic reticulum Ca2+ release channel ryanodine receptor (RyR2) plays a crucial role in aconitine-induced arrhythmias

“…Ca 2+ release from SR through the cardiac RyR 2 channel is a fundamental event in cardiac muscle contraction, which is triggered by calcium-induced calcium release (CICR) [11]. Alterations in the sensitivity of RyR 2 to Ca 2+ release activation have been implicated in diseases including malignant hyperthermia and heart failure [12][13][14].…”

Excitation-contraction coupling and mitochondrial energetics

“…During the action potential (AP), voltage-gated Na + -channels are activated, and the inward Na + -current (I Na ) induces a rapid depolarization of the cell membrane, facilitating voltage-dependent opening of L-type Ca 2+ -channels (I Ca,L ). The Ca 2+ influx triggers the opening of the ryanodine receptor (RyR2 subtype), inducing the release of even greater amounts of Ca 2+ from the sarcoplasmic reticulum (SR), a process termed Ca 2+ -induced Ca 2+ -release (CICR) [14,15,63,64]. The Ca 2+ released from RyRs floods the space between the SR and the cell membrane (i. e., the dyadic or junctional cleft), a gap of typically ∼10 nm and covering a volume with a radius of ∼200 nm [102,151].…”

Voltage‐dependence of ryanodine‐sensitive component of contraction in A23187‐ and isoprenaline‐treated cardiac muscles

“…Recently, in cardiac muscles, it has been proposed that Ca-induced Ca release is triggered by Ca flowing through Ca channels different from the slow channels (Fabiato, 1985a;Morad & Cleemann, 1987). This channel has been defined as a T-type of Ca channel (Hume & Giles, 1983;Bean, 1985;Nilius et al, 1985;Mitra & Morad, 1986).…”

“…From the recent studies on inward current. On the other hand, Fabiato (1985a), and Morad & Cleemann (1987) have proposed that Ca release may be triggered by Ca influx through fast Ca channels (corresponding to T-type of Ca channels), different from slow channels which have been described by Hume & Giles (1983), Bean (1985), Nilius et al (1985), and Mitra & Morad (1986). Thus, although Ca-induced Ca release may be a prevailing theory of cardiac excitationcontraction coupling, the exact role of Ca inward currents on the Ca-induced Ca release process in intact cardiac muscle is the subject of some controversy. Recently, the Ca ionophore, A23187, has been reported to produce two components of contraction each component of which could be separately observed by use of specific pharmacological interventions (Kondo, 1986).…”