Title

Maternal Diabetes Increases Large Conductance Ca2+-Activated K+ Outward Currents That Alter Action Potential Properties But Do Not Contribute To Attenuated Excitability Of Parasympathetic Cardiac Motoneurons In The Nucleus Ambiguus Of Neonatal Mice

Keywords

Afterhyperpolarization; Bk channels; Repolarization; Sk channels

Abstract

Previously, we demonstrated that maternal diabetes reduced the excitability and increased small-conductance Ca2+-activated K+ (SK) currents of parasympathetic cardiac motoneurons (PCMNs) in the nucleus ambiguous (NA). In addition, blockade of SK channels with apamin completely abolished this reduction. In the present study, we examined whether maternal diabetes affects large-conductance Ca2+-activated K+ (BK) channels and whether BK channels contribute to the attenuation of PCMN excitability observed in neonates of diabetic mothers. Neonatal mice from OVE26 diabetic mothers (NMDM) and normal FVB mothers (control) were used. The pericardial sac of neonatal mice at postnatal days 7-9 was injected with the tracer X-rhodamine-5 (and 6)-isothiocyanate 2 days prior to the experiment to retrogradely label PCMNs in the NA. Whole cell currentand voltage-clamps were used to measure spike frequency, action potential (AP) repolarization (half-width), afterhyperpolarization potential (AHP), transient outward currents, and afterhyperpolarization currents (IAHP). In whole cell voltage clamp mode, we confirmed that maternal diabetes increased transient outward currents and IAHP compared with normal cells. Using BK channel blockers charybdotoxin (CTx) and paxilline, we found that maternal diabetes increased CTx- and paxilline-sensitive transient outward currents but did not change CTx- and paxilline-sensitive IAHP. In whole cell current-clamp mode, we confirmed that maternal diabetes increased AP half-width and AHP, and reduced excitability of PCMNs. Furthermore, we found that after blockade of K channels with CTx or paxilline, maternal diabetes induced a greater increase of AP half-width but similarly decreased fast AHP without affecting medium AHP. Finally, blockade of BK channels decreased spike frequency in response to current injection in both control and NMDM without reducing the difference of spike frequency between the two groups. Therefore, we+onclude that although BK transient outward currents, which may alter AP repolarization, are increased in NMDM, BK channels+ do not directly contribute to maternal diabetes-induced attenuation of PCMN excitability. In contrast, based on evidence from our previous and present studies, reduction of PCMN excitability inneonates of diabetic mothers is largely dependent on altered SK current associated with maternal diabetes. © 2011 the American Physiological Society.

Publication Date

5-1-2011

Publication Title

American Journal of Physiology - Regulatory Integrative and Comparative Physiology

Volume

300

Issue

5

Number of Pages

-

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1152/ajpregu.00470.2010

Socpus ID

79955773120 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/79955773120

This document is currently not available here.

Share

COinS