Modulation of cardiac Na channels by angiotensin II

Nilius, Bernd; Tytgat, Jan; Albitz, R

doi:10.1016/0167-4889(89)90221-8

Cited by 18 publications

(8 citation statements)

References 10 publications

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“…The 41) is a slowing of inactivation kinetics. In heart muscle Na channels, on the other hand, the effects of PKC activation by phorbol ester and angiotensin II are different (42)(43)(44). The kinetic effects of Na channel phosphorylation appear to be complex and variable, perhaps because the number of potential phosphorylation sites in brain and muscle channels is very different.…”

Section: Discussionmentioning

confidence: 99%

Modulation of skeletal muscle sodium channels by human myotonin protein kinase.

Mounsey

John

et al. 1995

J. Clin. Invest.

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In myotonic muscular dystrophy, abnormal muscle Na currents underlie myotonic discharges. Since the myotonic muscular dystrophy gene encodes a product, human myotonin protein kinase, with structural similarity to protein kinases, we tested the idea that human myotonin protein kinase modulates skeletal muscle Na channels. Coexpression of human myotonin protein kinase with rat skeletal muscle Na channels in Xenopus oocytes reduced the amplitude of Na currents and accelerated current decay. The effect required the presence of a potential phosphorylation site in the inactivation mechanism of the channel. The mutation responsible for human disease, trinucleotide repeats in the 3' untranslated region, did not prevent the effect. The consequence of an abnormal amount of the kinase would be altered muscle cell excitability, consistent with the clinical finding of myotonia in myotonic dystrophy. (J. Clin. Invest. 1995. 95:2379-2384

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Section: Discussionmentioning

confidence: 99%

Modulation of skeletal muscle sodium channels by human myotonin protein kinase.

Mounsey

John

et al. 1995

J. Clin. Invest.

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“…However, angiotensin II activates PKC in the heart and has multiple modulatory effects on Na+ currents in cardiac myocytes (23)(24)(25). Some of these effects may result from activation ofPKC.…”

Section: Resultsmentioning

confidence: 99%

Modulation of cardiac Na+ channels expressed in a mammalian cell line and in ventricular myocytes by protein kinase C.

Rogers

Tanada

et al. 1994

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

105

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Cardiac rH1 Na+ channel a subunits were expressed in cells of the Chinese hamster lung 1610 cell line by transfection, and a stable cell line exprsing cardiac Na+ channels (SNa-rHl) was isolated. Mean Na+ currents of 2.2 ± 1.0 nA were recorded, which corresponds to a cell surface density of approximately 1-2 channels active at the peak of the Na+ current per pam2. The expressed cardiac Na+ current was tetrodotoxin resistant (Kd = 1.8 FM) and had voltagedependent properties similar to those of the Na+ current in neonatal ventricular myocytes. Activation of protein kinase C by 1-oleoyl-2-acetyl-sn-glycerol (OAG) (10 saM) decreased this current -33% at a holding potential of -114 mV and 56% at -94 mV. This reduction in peak current was caused in part by an 8-to 14-mV shift of steady-state inactivation in the hyperpolarized direction. Na+ channel activation was unchanged. Effects of OAG in SNa-rH1 cells and in neonatal rat cardiac myocytes were similar, except that the time course of inactivation was slowed either transiently or persistently when protein kinase C was activated in myocytes bathed in low-Ca2+ (1 M) or Ca2+-free solution but was unaffected in SNa-rH1 cells. The effects of OAG on cardiac Na+ current were blocked in cells that had been previously microlijected with a peptide inhibitor of protein kinase C but not with a peptide inhibitor of cAMP-dependent protein kinase, indicating that protein kinase C is responsible for the effects of OAG. Single-channel recordings from SNa-rHi cells showed that the probability of channel opening was reduced by OAG, but the conductance was unaffected. OAG did not induce the late Na+ channel openings observed with PKC modulation ofneuronal and skeletal muscle Na+ channels. Thus, the substantial reduction in Na+ current at normal diastolic depolarizations with 10 pM OAG is due to failure of channel opening in response to depolarization. Such Na+ current reductions may have profound effects on cardiac cell excitability.The rapid upstroke of the cardiac action potential due to the Na+ current through voltage-dependent Na+ channels is responsible for the rapid spread of activation through the atria and ventricles that initiates and coordinates contraction of the heart. Cardiac function depends critically on the amplitude, timing, and voltage dependence of the Na+ current, and interventions that modulate Na+ current have potent physiological effects. The functional properties of mammalian cardiac Na+ channels are distinctive. They are less sensitive to tetrodotoxin (TTX) than most Na+ channels, with a Kd of approximately 1-10 ,uM (1), and their kinetics of activation and inactivation are slower and more complex (2). These properties are mediated by a distinct Na+ channel a subunit (rH1) that was originally characterized by cloning from newborn rat heart (3) and denervated rat skeletal muscle (4). A closely related Na+ channel has been described in human cardiac muscle (5). Expression of these a subunit cDNAs in Xenopus oocytes (5-7) yields Na+ currents with functiona...

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“…Ang II increases the rate of diastolic depolarization and spontaneous discharges in human atrial tissues (Chen, Chang, Chiang, Cheng & Lin, 1991), a result that suggests that membrane currents are affected. Indeed, Ang II can facilitate a Ca2+ current (Freer et al 1976; Allen, Cohen, Dhallan, Gaa, Lederer & Rogers, 1988), leading to the elevation of [Ca2+]i (Kem et al 1991;Xu, Sandirasegarane & Gopalakrishnan, 1993), and a Na+ current (Nilius, Tytgat & Albitz, 1989;Moorman, Kirsch, Lacerda & Brown, 1989;Benz, Herzig & Kohlhardt, 1992). However, the effects of Ang II on other membrane currents have not been thoroughly investigated.…”

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confidence: 99%

Angiotensin II activation of a chloride current in rabbit cardiac myocytes.

Morita

Kimura

Endoh

1995

The Journal of Physiology

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1. The effects of angiotensin II (Ang II) on membrane currents were investigated in single ventricular myocytes from the rabbit heart by the whole-cell voltage-clamp method. 2. In the presence of an inhibitor of Ca2+ currents (nifedipine at 3 ,UM or CdCl2 at 0 3 mM) and a f6-adrenoceptor blocker (bupranolol at 1 /LM), 1 /uM Ang II significantly increased the membrane conductance.3. After elimination of K+ from external and internal solutions and its replacement by Cs+, Ang II at 041 /M increased an outwardly rectifying current that reached a maximum after about 40 min. The effect was concentration dependent (10-9_10-6 M) and was inhibited by saralasin, an antagonist of Ang II receptors.4. The reversal potential of the Ang II-induced current in the absence of K+ was compatible with the CF_ equilibrium potential at various external concentrations of CF-.5. A Cl-channel blocker, 4,4'-dinitrostilbene-2,2'-disulphonic acid (DNDS, at 5 mM), reversibly decreased the Ang II-induced current. 6. The Ang II-induced current developed when the internal solution contained Ca2+ (pCa 7 2 or 7 0) but not when it contained 10 mm EGTA without Ca2+.7. Besides developing a Cl-current, Ang II at 1 ,UM increased the inwardly rectifying K+ current (IK1) and this effect reached maximum within 3 min. 8. The effect of Ang II on the action potential was biphasic: the duration of the action potential was initially reduced and then it was increased. 9. These results suggest that Ang II induces a Cl-current that appears likely to modulate the action potential in rabbit ventricular myocytes.

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Modulation of cardiac Na channels by angiotensin II

Cited by 18 publications

References 10 publications

Modulation of skeletal muscle sodium channels by human myotonin protein kinase.

Modulation of skeletal muscle sodium channels by human myotonin protein kinase.

Modulation of cardiac Na+ channels expressed in a mammalian cell line and in ventricular myocytes by protein kinase C.

Angiotensin II activation of a chloride current in rabbit cardiac myocytes.

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