title: Modulation of synaptic transmission to second-order peripheral chemoreceptor neurons in caudal nucleus tractus solitarius by alpha1-adrenoreceptors.
abstract: Norepinephrine (NE) is an important neurotransmitter in central autonomic regulation. Peripheral chemoreceptor stimulation activates central noradrenergic structures. These structures innervate and therefore could modulate neurons in caudal nucleus tractus solitarius (cNTS), which receives the first central projections from peripheral chemoreceptors. However, the role of alpha(1)-adrenoreceptors in synaptic transmission of peripheral chemoreceptor inputs in cNTS is unknown. We investigated the responses to activation of alpha(1)-adrenoreceptors on glutamatergic and GABAergic inputs in NTS slices using whole-cell recording. Second-order neurons were identified by 1,1'-dilinoleyl-3,3,3',3'-tetra-methylindocarbocyanine, 4-chlorobenzenesulphonate (DiA) labeling of carotid bodies. Electrical stimulation of ipsilateral tractus solitarius was used to evoke excitatory postsynaptic currents (eEPSCs), whereas inhibitory postsynaptic currents were evoked (eIPSCs) by electrically stimulating NTS near the recorded neuron. Application of alpha(1)-adrenoreceptor agonist phenylephrine (PE) at 20 microM significantly decreased amplitudes of eEPSCs (78 +/- 1% of control; n = 16; p < 0.01), and it increased amplitudes of eIPSCs (120 +/- 13% of control; n = 7; p < 0.01). Both effects were blocked by the alpha(1)-adrenoreceptor antagonist prazosin at 10 microM. PE did not change holding current, input resistance, and current-voltage relationship in cNTS neurons. PE significantly changed paired pulse ratios of eEPSC/eIPSCs, increased the frequency of miniature IPSCs (329 +/- 10% of control; n = 6; p < 0.05), but it decreased that of miniature EPSCs (69 +/- 6% of control; n = 5; p < 0.01). PE-induced inhibition of eEPSCs was independent of N-methyl-D-aspartate or GABA(B) receptors. These results suggest that activation of alpha(1)-adrenoreceptors reduces excitatory and enhances inhibitory inputs to second-order peripheral chemoreceptor neurons in cNTS via a presynaptic mechanism. These actions result in the inhibition of synaptic transmission and could play a role in the autonomic responses to hypoxia.
authors.affiliation: Department of Pharmacology, The University of Texas Health Science Center at San Antonio, TX 78229-3900, USA.
authors.forename: Weirong
authors.initials: W
authors.lastname: Zhang
authors.forename: Steve W
authors.initials: SW
authors.lastname: Mifflin
mesh_terms: D000818:Animals; D002628:Chemoreceptor Cells / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D018080:Receptors, GABA-B / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D017552:Solitary Nucleus / Q000502:physiology*; D009435:Synaptic Transmission
chemical_list: D018340:Receptors, Adrenergic, alpha-1; D018080:Receptors, GABA-B; D016194:Receptors, N-Methyl-D-Aspartate; D010656:Phenylephrine