The calcium and frequency dependence of the slow inward current ‘staircase’ in frog atrium.

Noble, S J; Shimoni, Y.

doi:10.1113/jphysiol.1981.sp013537

Cited by 77 publications

(44 citation statements)

References 51 publications

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“…Furthermore he presents evidence that the slow rise of force during the staircase is the result of a progressive increase of Ca2+ inflow with each beat. A rate-dependent increase in the Ca2+ current has indeed been observed by a number of authors (Noble & Shimoni, 1981;Payett, Schanne & Ruiz-Ceretti, 1981;Boyett & Fedida, 1984). Bers (1985) argues that this hypothesis is not inconsistent with a role for aka, because part of the Ca2+ inflow may be via Na+ efflux-Ca2+ influx exchange and a rise of a'a may potentiate this.…”

Section: Ca2+ Loading Via the Ca2+ Currentmentioning

confidence: 83%

Effects of repetitive activity on developed force and intracellular sodium in isolated sheep and dog Purkinje fibres.

Boyett

Hart

Levi

et al. 1987

The Journal of Physiology

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SUMMARY1. When cardiac muscle is stimulated after a rest there is a gradual increase in force development over several minutes. The origin of this 'force staircase' was investigated in experiments on sheep and dog Purkinje fibres. Particular attention was paid to the possible role of changes in the intracellular Na+ activity (aNa).2. The first line of evidence for a role for aka came from a comparison of sheep and dog Purkinje fibres generating action potentials: after a change in the stimulus rate the slow changes of both a'a and force were monophasic in sheep but biphasic in dog preparations.3. In the remaining experiments changes in aia and force in sheep preparations were measured during 4 min trains of voltage-clamp pulses at a frequency of 2-5 Hz.4. A number of these voltage-clamp experiments also indicated that changes in aka are involved. Depending on the preparation and the duration of the pulses aka rose or fell during a train -a rise in a'a was always associated with a gradual rise in force, whereas a fall in aka was usually accompanied by a gradual fall in force.The addition of tetrodotoxin (TTX) or the use of a low holding potential reduced the progressive rises of both a'a and force, whereas the inclusion of a 10 mV hyperpolarization between pulses potentiated the progressive rises of both.5. The effect of TTX on the staircase was more marked the longer the pulses during the train; this possibly indicates that the effect of aNa on the force staircase is complex and is more marked with longer pulses. 6. A rise in aia was shown not to be the only factor underlying the progressive increase in force, because in many preparations a gradual rise in force occurred in spite of no change or even a fall of aNa.7. It is concluded that an increase in aka is involved in the slow increase in force during the staircase accompanying a train of action potentials, and that other factors are also involved; various possibilities are discussed.

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Section: Ca2+ Loading Via the Ca2+ Currentmentioning

confidence: 83%

Effects of repetitive activity on developed force and intracellular sodium in isolated sheep and dog Purkinje fibres.

Boyett

Hart

Levi

et al. 1987

The Journal of Physiology

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“…Calcium channels also show facilitation with an increase in depolarization frequency (5,6). In this paradigm, facilitation depends on Ca 2+ influx and an intact sequence around the IQ motif in the carboxy-terminus of the Ca V 1.2 channel (12-14, 19-22, 33).…”

Section: Resultsmentioning

confidence: 99%

Facilitation of murine cardiac L-type Ca _v 1.2 channel is modulated by Calmodulin kinase II–dependent phosphorylation of S1512 and S1570

Blaich

Welling

Fischer

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Activity-dependent means of altering calcium (Ca 2+ ) influx are assumed to be of great physiological consequence, although definitive tests of this assumption have only begun to emerge. Facilitation and inactivation offer two opposing, activity-dependent means of altering Ca 2+ influx via cardiac Ca v 1.2 calcium channels. Voltage-and frequency-dependent facilitation of Ca v 1.2 has been reported to depend on Calmodulin (CaM) and/or the activity of Calmodulin kinase II (CaMKII). Several sites within the cardiac Ltype calcium channel complex have been proposed as the targets of CaMKII. Here, we generated mice with knockin mutations of α 1 1.2 S1512 and S1570 phosphorylation sites [sine facilitation (SF) mice]. Homocygote SF mice were viable and reproduced in a Mendelian ratio. Voltage-dependent facilitation in ventricular cardiomyocytes carrying the SF mutation was decreased from 1.58-to 1.18-fold. The CaMKII inhibitor KN-93 reduced facilitation to 1.28 in control cardiomyocytes. SF mutation negatively shifted the voltage-dependent inactivation and slowed recovery from inactivation, thereby making fewer channels available for activation. Telemetric ECG recordings at different heart rates showed that QT time decreased significantly more in SF than in control mice at higher rates. Our results strongly support the notion that CaMKII-dependent phosphorylation of Cav1.2 at S1512 and S1570 mediates Ca 2+ current facilitation in the murine heart. calcium channels | facilitation | heart | voltage-dependent ion channels C alcium (Ca 2+ ) current (I Ca ) through L-type channels is an important determinant of intracellular Ca 2+ transients that trigger transmitter release, secretion, and contraction (1). In the heart, the size of the intracellular Ca 2+ transient is determined by the release of Ca 2+ from intracellular stores and by the size of the L-type current (2). The availability of L-type channels to open is regulated by the membrane potential and other factors that include protein kinases, phosphatases, and Ca 2+ binding proteins (3, 4). A train of repetitive depolarizations (frequency-dependent) (5, 6) or a strong depolarizing prepulse (voltage-dependent) (7) drives the L-type calcium channels from their normal gating pattern into a mode of gating characterized by long opening and high open probability (8, 9), a process that has been termed "facilitation" and that represents one of the rare positive feedback mechanisms in signal transduction. The present consensus is that facilitation requires elevated intracellular calcium, or [Ca 2+ ], in the vicinity of the channel ("Ca In addition or alternatively to these CaM-dependent mechanisms, CDF of Ca v 1.2 has been attributed to the action of Calmodulin kinase II (CaMKII) (17)(18)(19)(20). Constitutively active CaMKII facilitated L-type current in excised patches (21). CaMKII is tethered to the C terminus in close proximity to the IQ motif, and CDF was abolished by mutating the putative interaction site (22). CaM-KII was reported by us and by others to phosphorylat...

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“…This was described first in frog atrium (Noble and Shimoni, 1981), and then in rat (Richard et al, 1990;Richard et al, 1993), guinea-pig (Mitra and Morad, 1986;Lee, 1987;Fedida et al, 1988a;Fedida et al, 1988b;Zygmunt and Maylie, 1990), rabbit (Hryshko and Bers, 1990), ferret dog (Tseng, 1988) and human (Piot et al, 1996) cardiomyocytes, although a pronounced decrease of I Ca has been observed in mouse (Sipido et al, 1998b) in which the decrease might reflect insufficient time to recover from voltage dependent inactivation.…”

Section: Facilitationmentioning

confidence: 97%

Ca2+ currents in cardiac myocytes: Old story, new insights

Brette

Leroy

Guennec

et al. 2006

Progress in Biophysics and Molecular Biology

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The calcium and frequency dependence of the slow inward current ‘staircase’ in frog atrium.

Cited by 77 publications

References 51 publications

Effects of repetitive activity on developed force and intracellular sodium in isolated sheep and dog Purkinje fibres.

Effects of repetitive activity on developed force and intracellular sodium in isolated sheep and dog Purkinje fibres.

Facilitation of murine cardiac L-type Ca _v 1.2 channel is modulated by Calmodulin kinase II–dependent phosphorylation of S1512 and S1570

Ca2+ currents in cardiac myocytes: Old story, new insights

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The calcium and frequency dependence of the slow inward current ‘staircase’ in frog atrium.

Cited by 77 publications

References 51 publications

Effects of repetitive activity on developed force and intracellular sodium in isolated sheep and dog Purkinje fibres.

Effects of repetitive activity on developed force and intracellular sodium in isolated sheep and dog Purkinje fibres.

Facilitation of murine cardiac L-type Ca v 1.2 channel is modulated by Calmodulin kinase II–dependent phosphorylation of S1512 and S1570

Ca2+ currents in cardiac myocytes: Old story, new insights

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Facilitation of murine cardiac L-type Ca _v 1.2 channel is modulated by Calmodulin kinase II–dependent phosphorylation of S1512 and S1570