Blunted sensitivity of intracardiac ganglion neurons to nicotine in type‐2 diabetic rats

Abstract

Acetylcholine, a principal excitatory neurotransmitter at the intracardiac ganglionic synapse, acts on the nicotinic acetylcholine receptors (nAChRs) and induces the cell excitation in intracardiac ganglion (ICG) neurons. Our previous study showed that ICG neuron excitability was lowered by the decreased Ca2+ currents in high‐fat diet/low‐dose streptozotocin‐induced type‐2 diabetes mellitus (T2DM) rats. In the present study, we examined the effect of nicotine (a nAChR agonist) on Ca2+ currents and cell excitability in ICG neurons from sham and T2DM rats. Immunofluorescence data showed that there was no significant difference on the protein expression of nAChRs in ICG neurons from sham and T2DM rats. Using whole‐cell patch clamp technique, we found that nicotine concentration‐dependently increased ICG neuron excitation (action potential frequency) and the sensitivity of ICG neuron to nicotine in diabetic rats was lower than that in sham rats (EC50 value is 2.86 μM in T2DM rats and 0.48 μM in sham rats). Diabetes also decreased the response of Ca2+ channels to nicotine in ICG neurons, compared to sham rats. In addition, nicotinic receptor antagonist (100 μM hexamethonium) completely blocked the effect of nicotine on ICG neuron excitability and Ca2+ currents in sham and T2DM rats. Our results indicate that T2DM decreases the sensitivity of ICG neurons to nicotine.