RESUMEN
At the end of pregnancy, the uterus transitions from a quiescent to a highly contractile state. This is partly due to depolarization of the resting membrane potential in uterine (myometrial) smooth muscle cells (MSMCs). Experiments with human MSMCs showed that the membrane potential is regulated by a functional complex between the sodium (Na+)-activated potassium (K+) channel SLO2.1 and the Na+ Leak Channel Non-Selective (NALCN). In human MSMCs, Na+ entering through NALCN activates SLO2.1, leading to K+ efflux, membrane hyperpolarization (cells become more negative inside), and reduced contractility. Decreased SLO2.1/NALCN activity results in reduced K+ efflux, leading to membrane depolarization, Ca2+ influx via voltage-dependent calcium channels, and increased MSMC contractility. However, all of these experiments were performed with MSMCs isolated from women at term, so the role of the SLO2.1/NALCN complex early in pregnancy was speculative. To address this question here, we examined the role of the SLO2.1/NALCN complex in regulating mouse MSMC membrane potential across pregnancy. We report that Slo2.1 and Nalcn expression change along pregnancy, being more highly expressed in MSMCs from non-pregnant and early pregnant mice than in those from late-pregnant mice. Functional studies revealed that SLO2.1 channels mediate a significant portion of the K+ current in mouse MSMCs, particularly in cells from non-pregnant and early pregnant mice. Activation of SLO2.1 by Na+ influx through NALCN led to membrane hyperpolarization in MSMCs from early pregnancy but not in MSMCs from later pregnancy. Moreover, we found that the NALCN/SLO2.1 complex regulates intracellular Ca2+ responses more in MSMCs from non-pregnant and early pregnancy mice than in MSMCs from late pregnancy. Together, these findings reveal that the SLO2.1/NALCN functional complex is conserved between mouse and humans and functions throughout pregnancy. This work could open avenues for targeted pharmacological interventions in pregnancy-related complications.
RESUMEN
Ileocolic intussusception is a consideration in young pediatric patients with acute abdominal pain. Meckel's diverticulum is the most common pathologic lead point for intussusception in children and the appendix acting as the lead point is rare. In addition, management guidelines for recurrent ileocolic intussusception (RICI) are lacking. We present two cases of RICI in which the pathological lead point was the appendix. The first patient, a two-year-old with no medical history, had intermittent abdominal pain and non-bloody vomiting for a month. Ultrasound revealed ileocolic intussusception, successfully managed with pneumatic reduction. However, symptoms recurred and a repeat ultrasound showed partial intussusception of the appendix into the cecum. Laparoscopic reduction and appendectomy were then performed. Symptomatic intussusception recurred, and a second laparoscopic reduction with stump appendectomy resolved all symptoms. The second patient, a three-year-old with no medical history, had colicky abdominal pain for 24 hours. Ultrasound revealed ileocolic intussusception that was pneumatically reduced. As pain recurred, laparoscopic reduction and appendectomy were performed, revealing ileocolic intussusception with a dilated appendix as the pathologic lead point. Recurrent ileocolic intussusception (RICI) with the appendix as the lead point is common, but RICI with the appendix as the lead point is rare. These cases demonstrate the role of the appendix as a pathologic lead point, and a review of the literature supports the need for surgical reduction. While enema reduction is the first line for recurrent intussusception, surgical reduction is preferred when a pathological lead point is suspected.
RESUMEN
To fertilize an oocyte, sperm must undergo several biochemical and functional changes known as capacitation. A key event in capacitation is calcium influx through the cation channel of sperm (CatSper). However, the molecular mechanisms of capacitation downstream of this calcium influx are not completely understood. Capacitation is also associated with an increase in mitochondrial oxygen consumption, and several lines of evidence indicate that regulated calcium entry into mitochondria increases the efficiency of oxidative respiration. Thus, we hypothesized that calcium influx through CatSper during capacitation increases mitochondrial calcium concentration and mitochondrial efficiency and thereby contributes to sperm hyperactivation and fertilization capacity. To test this hypothesis, we used high-resolution respirometry to measure mouse sperm mitochondrial activity. We also measured mitochondrial membrane potential, ATP/ADP exchange during capacitation, and mitochondrial calcium concentration in sperm from wild-type and CatSper knockout mice. We show that the increase in mitochondrial activity in capacitated wild-type sperm parallels the increase in mitochondrial calcium concentration. This effect is blunted in sperm from CatSper knockout mice. Importantly, these mechanisms are needed for optimal hyperactivation and fertilization in wild-type mice, as confirmed by using mitochondrial inhibitors. Thus, we describe a novel mechanism of sperm capacitation. This work contributes to our understanding of the role of mitochondria in sperm physiology and opens the possibility of new molecular targets for fertility treatments and male contraception.
