Maternal Diabetes Increases Small Conductance Ca Currents Which Alter Action Potential Properties and Excitability of Cardiac 2 Motoneurons in the Nucleus Ambiguus 3

27 Parasympathetic cardiac motoneurons (PCMNs) in the nucleus ambiguus (NA) 28 play a key role in regulating cardiac functions. In this study, we examine the effects of 29 maternal diabetes on excitability, action potential (AP) properties, and small 30 conductance Ca 2+-activated K + (SK) currents of PCMNs. Neonatal mice from diabetic 31 (OVE26 female, NMDM) and normal (FVB female, control) mothers which had been 32 mated with non-diabetic fathers (FVB male) were used. Tracer XRITC was injected 33 into the pericardial sac at P7-9 to retrogradely label PCMNs. Two days later, 34 XRITC-labeled PCMNs were identified in brainstem slices. The responses of spike 35 frequency, AP repolarization (half-width) and afterhyperpolarization (AHP) of 36 PCMNs to current injections were studied using whole-cell current clamp. Outward 37 currents and afterhyperpolarization currents (I AHP) in response to voltage steps were 38 measured using whole-cell voltage clamp. In examining the effect of maternal 39 diabetes on excitability and AP properties, we found that in NMDM spike frequency 40 decreased, the half-width and AHP peak amplitude increased, and the peak amplitude 41 of outward transient currents and I AHP increased compared to those measured in 42 control. In examining the effect of maternal diabetes on SK channels, we found that 43 after blockage of SK channels with a specific SK channel blocker apamin, maternal 44 diabetes significantly increased apamin-sensitive outward transient currents and I AHP , 45 and suppressed AHP amplitude in NMDM more than those in control. Further, 46 apamin application increased the firing rate to current injections and completely 47 4 abolished the difference of the firing rate between control and NMDM. We suggest 48 that the augmented SK-mediated currents may contribute to the increased AHP 49 amplitude and the attenuated excitability of PCMNs in NMDM.