Maternal Diabetes Increases Small Conductance Ca2+-activated K+ (SK) Currents That Alter Action Potential Properties and Excitability of Cardiac Motoneurons in the Nucleus Ambiguus

J Neurophysiol. 2010 Oct;104(4):2125-38. doi: 10.1152/jn.00671.2009. Epub 2010 Jul 28.

Abstract

Parasympathetic cardiac motoneurons (PCMNs) in the nucleus ambiguus (NA) play a key role in regulating cardiac functions. In this study, we examined the effects of maternal diabetes on excitability, action potential (AP) properties, and small conductance Ca(2+)-activated K(+) (SK) currents of PCMNs. Neonatal mice from diabetic (OVE26 female, NMDM) and normal (FVB female, control) mothers that had been mated with nondiabetic fathers (FVB male) were used. Tracer XRITC was injected into the pericardial sac at P7-9 to retrogradely label PCMNs. Two days later, XRITC-labeled PCMNs were identified in brain stem slices. The responses of spike frequency, AP repolarization (half-width) and afterhyperpolarization (AHP) of PCMNs to current injections were studied using whole cell current clamp. Outward and afterhyperpolarization currents (I(AHP)) in response to voltage steps were measured using whole cell voltage clamp. In examining the effects of maternal diabetes on excitability and AP properties, we found that in NMDM spike frequency decreased, the half-width and AHP peak amplitude increased, and the peak amplitude of outward transient currents and I(AHP) increased compared with those measured in control. In examining the effects of maternal diabetes on SK channels, we found that after blockage of SK channels with a specific SK channel blocker apamin, maternal diabetes significantly increased apamin-sensitive outward transient currents and I(AHP), and suppressed AHP amplitude in NMDM more than those in control. Further, apamin application increased the firing rate to current injections and completely abolished the difference of the firing rate between control and NMDM. We suggest that the augmented SK-mediated currents may contribute to the increased AHP amplitude and the attenuated excitability of PCMNs in NMDM.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Animals, Newborn
  • Female
  • Male
  • Medulla Oblongata / physiology*
  • Membrane Potentials / physiology
  • Mice
  • Mice, Transgenic
  • Motor Neurons / pathology
  • Motor Neurons / physiology*
  • Pregnancy
  • Pregnancy in Diabetics / metabolism*
  • Pregnancy in Diabetics / pathology
  • Pregnancy in Diabetics / physiopathology*
  • Small-Conductance Calcium-Activated Potassium Channels / physiology*

Substances

  • Small-Conductance Calcium-Activated Potassium Channels