In unexcitable, noncardiac cells, ultrashort (nanosecond) high-voltage (megavolt-per-meter) pulsed electrical fields (nsPEF) can mobilize intracellular Ca2+ and create transient nanopores in the plasmalemma. We studied Ca2+ responses to nsPEF in cardiac cells. Fluorescent Ca2+ or voltage signals were recorded from isolated adult rat ventricular myocytes deposited in an electrode microchamber and stimulated with conventional pulses (CPs; 0.5-2.4 kV/cm, 1 ms) or nsPEF (10-80 kV/cm, 4 ns). nsPEF induced Ca2+ transients in 68/104 cells. Repeating nsPEF increased the likelihood of Ca2+ transient induction (61.8% for <10 nsPEF vs. 80.6% for > or =10 nsPEF). Repetitive Ca2+ waves arising at the anodal side and Ca2+ destabilization occurred after repeated nsPEF (12/29) or during steady-state single nsPEF delivery at 2 Hz. Removing extracellular Ca2+ abolished responses to nsPEF. Verapamil did not affect nsPEF-induced Ca2+ transients, but decreased responses to CP. Tetrodotoxin and KB-R7943 increased the repetition threshold in response to nsPEF: 1-20 nsPEF caused local anodal Ca2+ waves without Ca2+ transients, and > or =20 nsPEF caused normal transients. Ryanodine-thapsigargin and caffeine protected against nsPEF-induced Ca2+ waves and showed less recovery of diastolic Ca2+ levels than CP. Voltage recordings demonstrated action potentials triggered by nsPEF, even in the presence of tetrodotoxin. nsPEF can mobilize intracellular Ca2+ in cardiac myocytes by inducing action potentials. Anodal Ca2+ waves and resistance to Na+ and Ca2+ channel blockade suggest nonselective ion channel transport via sarcolemmal nanopores as a triggering mechanism.

Background: The autonomic nervous system response to apnea and its mechanistic connection to atrial fibrillation (AF) are unclear. We hypothesize that sensory neurons within the ganglionated plexi (GP) play a role. We aimed to delineate the autonomic response to apnea and to test the effects of ablation of cardiac sensory neurons with resiniferatoxin (RTX), a neurotoxic TRPV1 (transient receptor potential vanilloid 1) agonist. Methods Sixteen dogs were anesthetized and ventilated. Apnea was induced by stopping ventilation until oxygen saturations decreased to 80%. Nerve recordings from bilateral vagal nerves, left stellate ganglion, and anterior right GP were obtained before and during apnea, before and after RTX injection in the anterior right GP (protocol 1, n=7). Atrial effective refractory period and AF inducibility on single extrastimulation were assessed before and during apnea, and before and after intrapericardial RTX administration (protocol 2, n=9). GPs underwent immunohistochemical staining for TRPV1. Results: Apnea increased anterior right GP activity, followed by clustered crescendo vagal bursts synchronized with heart rate and blood pressure oscillations. On further oxygen desaturation, a tonic increase in stellate ganglion activity and blood pressure ensued. Apnea-induced effective refractory period shortening from 110.20±31.3 ms to 90.6±29.1 ms ( P <0.001), and AF induction in 9/9 dogs versus 0/9 at baseline. After RTX administration, increases in GP and stellate ganglion activity and blood pressure during apnea were abolished, effective refractory period increased to 126.7±26.9 ms ( P =0.0001), and AF was not induced. Vagal bursts remained unchanged. GP cells showed cytoplasmic microvacuolization and apoptosis. Conclusions: Apnea increases GP activity, followed by vagal bursts and tonic stellate ganglion firing. RTX decreases sympathetic and GP nerve activity, abolishes apnea’s electrophysiological response, and AF inducibility. Sensory neurons play a role in apnea-induced AF.

Nutrient restriction (NR) prolongs longevity via enhanced mitochondrial function. To test the hypothesis that NR enhances resistance to ischemia/reperfusion (IR) arrhythmias via preserved calcium (Ca) cycling and mitochondrial function. We examined the protective effects of NR on regional IR in cultured neonatal rat ventricular myocyte monolayers. Optical mapping of intracellular Ca and mitochondrial membrane potential Δψm was performed using Rhod 2-AM and TMRE, respectively. Regional ischemia was mimicked by covering a portion of monolayer with a glass coverslip until loss of Ca propagation, and reperfusion was mimicked by removing the coverslip. NR was mimicked by culture in serum- and glucose-free medium for 24 hours. Relative to controls, NR monolayers sustained Ca oscillations during longer periods of ischemia (19.2±1.8 min vs 10.4±1.4 min, p < 0.001); attenuated increases in Ca transient duration (CaD) and time decay Constant (Tau) during ischemia; preserved Conduction velocity (CV) during early reperfusion, leading to protection against reperfusion arrhythmias; had minimal “rebound” decreased CaD and Tau during reperfusion; and had no depolarization of Δψm during IR. NR attenuates IR arrhythmias via 1) stable calcium cycling; and 2) prevention of Δψm depolarization during IR. Enhanced mitochondrial resistance to IR arrhythmias may play a role in NR-induced longevity prolongation.

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The “double reduction” policy is an important measure to implement the Party’s education policy. It is of great significance for fulfilling the fundamental task of life and fostering people, comprehensively improving the quality of school education and teaching, as well as promoting the comprehensive and healthy growth of young people. In order to implement the “double reduction” policy, schools are facing many problems. Beginning with classroom teaching, schools need to entrust students with the main position of the classroom. This is not only a challenge but also an opportunity for schools to deepen the reform of education and teaching.