cardiovascular system
• echocardiography shows a slightly reduced heart rate of about 10% and moderately increased (about 20%) left ventricular wall thickness
• however, ejection fraction, fractional shortening, stroke volume and cardiac output are unchanged
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• heart rate is reduced about 10%
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• none of the common stimulation protocols (a burst pacing, a long pause, and a short-coupled premature ventricular complex) reliably induce ventricular arrhythmias in mutant mice
• however, a protocol consisting of a long-burst, long-pause, and short-coupled extra-stimulus (LBLPS) consistently triggers ventricular arrhythmias in mutants but not wild-type mice
• mice pretreated with quinidine sulfate reduces the duration and incidence of LBLPS-evoked polymorphic ventricular arrhythmias
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• elevating extracellular calcium concentration to promote sarcoplasmic reticulum calcium overload, induces little or no calcium waves in hearts
• hearts show resilience to caffeine- and epinephrine-promoted spontaneous calcium waves
• at high stimulation frequencies, hearts are more prone to calcium alternans and exhibit prolonged calcium release refractoriness
• however, the amplitude, time to peak, and decay time of depolarization-induced calcium transients at low stimulation frequency in hearts or isolated cardiomyocytes are similar to wild-type mice
• ventricular myocytes show an electrophysiological remodeling of surface membrane currents
• the Na/Ca exchange current is substantially augmented in ventricular myocytes
• the transient outward potassium current density and voltage-dependent activation are enhanced in ventricular myocytes
• ventricular myocytes are highly susceptible to early afterdepolarizations
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• L-type calcium channel current density in ventricular myocytes is enhanced
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• the sodium current shows a leftward (hyperpolarization) shift in voltage-dependent activation and inactivation in ventricular myocytes
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• a mixture of a high dose of caffeine and epinephrine does not promote ventricular arrhythmias as in wild-type mice, indicating protection of heart against stress-induced ventricular arrhythmias
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homeostasis/metabolism
• a mixture of a high dose of caffeine and epinephrine does not promote ventricular arrhythmias as in wild-type mice, indicating protection of heart against stress-induced ventricular arrhythmias
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nervous system
• ventricular myocytes exhibit an altered action potential waveform with a shorter action potential duration at 50% and prolonged action potential duration at 90%, however the action potential amplitude and resting membrane potential are unchanged
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
heart disease | DOID:114 | J:302151 |