Heterogeneous functional expression of calcium channels at sensory and synaptic regions in nodose neurons

Abstract

1. In the present study we have taken advantage of the unique anatomy of visceral sensory neurons that enabled us to isolate and examine the role of calcium channel subtypes at the soma, central synaptic terminals, and peripheral sensory endings. 2. N-type calcium channels dominated somatic currents (60%), with lesser (16% and 12%) contributions from P- and L-type channels, respectively, in patch-clamped dispersed nodose neurons using toxins selective for each calcium channel subtype. 3. These toxins also blocked the release of neurotransmitters from these visceral synaptic terminals in a brain stem slice. Similar to the profile at the soma, N-type calcium channels were most responsible for neurotransmission at this central glutamatergic synapse (57%), with P- and L-type channels making small contributions (12% and 11%, respectively). 4. In contrast to the soma and central synapses, these calcium channel toxins failed to affect the sensory transduction at aortic baroreceptor endings. 5. Therefore calcium channel subtypes have dramatically heterogenous distributions in sensory neurons that presumably subserve the specialized functions that occur at different cellular regions.

Differential behavioral state-dependence in the burst properties of CA3 and CA1 neurons

“…This effect has been partly attributed to elevated intracellular Ca 2ϩ from activation of the LTCC. In hippocampal and cerebellar Purkinjie neurons and some sensory neurons, LTCCs may also contribute to normal functions of neurotransmitter release (95)(96)(97)(98)(99). A slower deactivation LTCC tail current in the presenilin mutants during recovery from stress-inducing treatments will result in elevated Ca 2ϩ influx and increased release probability of synaptic vesicles, which is consistent with our observation of the increased EJC amplitude (Supplemental Fig.…”

Ketamine Differentially Blocks Sensory Afferent Synaptic Transmission in Medial Nucleus Tractus Solitarius (mNTS)

“…We believe that these nodose properties most likely closely reflect the properties of the axons entering the brain stem to synapse on mNTS neurons as has been observed previously. 44 Therefore, the correlation between peripheral (nodose ganglion) and central (NTS slice) responses of these afferents offers a consistent view of the presynaptic element in afferent synaptic transmission. 24 NMDA receptors were activated in a specific minority of neurons (a small subgroup of capsaicinresistant mNTS neurons), and these were much more sensitive to ketamine than the synaptic failure.…”

Colonic smooth muscle cells and colonic motility patterns as a target for irritable bowel syndrome therapy: mechanisms of action of otilonium bromide

“…An inhibition of tachikinergic signaling by OB could thus reduce abdominal pain and discomfort in patients with IBS. Likewise, L-type Ca 2+ channels are expressed by dorsal root ganglia which provide sensory innervation to the gut [Mendelowitz et al 1995]. In animal models, IBS evoked upregulation of L-type Ca 2+ channels while their pharmacological blockade inhibited visceral pain, indicating involvement of the channel in hypersensitivity [Qian et al 2013].…”