Na+-Leak Channel, Non-Selective (NALCN) Regulates Myometrial Excitability and Facilitates Successful Parturition
| Autor: | Yong Wang, Sarah K. England, Peinan Zhao, Chinwendu Amazu, K. Joseph Hurt, Wenjie Wu, Xiaofeng Ma, Erin L. Reinl, Rachael Bok |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Leak Patch-Clamp Techniques Physiology Action Potentials Nerve Tissue Proteins Article lcsh:Physiology Andrology lcsh:Biochemistry 03 medical and health sciences Mice Uterine Contraction Pregnancy Current clamp Myosin Medicine Animals lcsh:QD415-436 Ion channel Mice Knockout NALCN lcsh:QP1-981 business.industry Spike density Uterus Myometrium Parturition Membrane Proteins Muscle Smooth medicine.disease Mice Inbred C57BL 030104 developmental biology Ion channels Knockout mouse Female business Uterine excitability |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 48, Iss 2, Pp 503-515 (2018) Cell Physiol Biochem |
| ISSN: | 1421-9778 1015-8987 |
| Popis: | Background/Aims: Uterine contractility is controlled by electrical signals generated by myometrial smooth muscle cells. Because aberrant electrical signaling may cause inefficient uterine contractions and poor reproductive outcomes, there is great interest in defining the ion channels that regulate uterine excitability. In human myometrium, the Na+ leak channel, non-selective (NALCN) contributes to a gadolinium-sensitive, Na+-dependent leak current. The aim of this study was to determine the role of NALCN in regulating uterine excitability and examine its involvement in parturition. Methods: Wildtype C57BL/6J mice underwent timed-mating and NALCN uterine expression was measured at several time points across pregnancy including pregnancy days 7, 10, 14, 18 and 19. Sharp electrode current clamp was used to measure uterine excitability at these same time points. To determine NALCN’s contribution to myometrial excitability and pregnancy outcomes, we created smooth-muscle-specific NALCN knockout mice by crossing NALCNfx/fx mice with myosin heavy chain Cre (MHCCreeGFP) mice. Parturition outcomes were assessed by observation via surveillance video recording cre control, flox control, smNALCN+/-, and smNALCN-/- mice. Myometrial excitability was compared between pregnancy day 19 flox controls and smNALCN-/- mice. Results: We found that in the mouse uterus, NALCN protein levels were high early in pregnancy, decreased in mid and late pregnancy, and then increased in labor and postpartum. Sharp electrode current clamp recordings of mouse longitudinal myometrial samples from pregnancy days 7, 10, 14, 18, and 19 revealed day-dependent increases in burst duration and interval and decreases in spike density. NALCN smooth muscle knockout mice had reduced myometrial excitability exemplified by shortened action potential bursts, and an increased rate of abnormal labor, including prolonged and dysfunctional labor. Conclusions: Together, our findings demonstrate that the Na+ conducting channel NALCN contributes to the myometrial action potential waveform and is important for successful labor outcomes. |
| Databáze: | OpenAIRE |
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