Group I Metabotropic Glutamate Receptors on Second-Order Baroreceptor Neurons Are Tonically Activated and Induce a Na⁺–Ca²⁺Exchange Current

Abstract

Sekizawa, Shin-ichi and Ann C. Bonham. Group I metabotropic glutamate receptors on second-order baroreceptor neurons are tonically activated and induce a Na ϩ -Ca 2ϩ exchange current. J Neurophysiol 95: 882-892, 2006. First published September 28, 2005 doi:10.1152/jn.00772.2005. The nucleus tractus solitarius (NTS) is essential for coordinating baroreflex control of blood pressure. The baroreceptor sensory fibers make glutamatergic synapses onto secondorder NTS neurons. Glutamate spillover activates Group II and III presynaptic metabotropic glutamate receptors (mGluRs) on the baroreceptor central terminals to inhibit synaptic transmission, but the role of postsynaptic mGluRs is less understood. We used whole cell patch-clamping in anatomically identified second-order baroreceptor neurons in a brain stem slice to test whether Group I, II, and III mGluRs had postsynaptic effects at this first central synapse in the baroreceptor afferent pathway. The Group I agonist DHPG induced a depolarization and spiking that was mimicked by endogenous glutamate. Group I mGluR blockade prevented the depolarization and slightly hyperpolarized the neurons, suggesting a small tonic Group I mGluR activation. The DHPG-induced inward current consisted of voltage-dependent and -independent components; the former was blocked by TEA and the latter was blocked by replacing extracellular NaCl with LiCl or Tris-HCl. The DHPG current was potentiated in a Ca 2ϩ -free external solution and was diminished by intracellular dialysis with BAPTA and by perfusion with Na ϩ -Ca 2ϩ exchanger blockers, KB-R7943 or 3Ј,4Ј-dichlorobenzamil. Intracellular dialysis with GDP␤S or heparin and perfusion with the PLC inhibitor U-73122 or the Ca 2ϩ -calmodulin inhibitor W-7 significantly decreased the DHPG current. The data suggest that Group I mGluRs on baroreceptor neurons are functional; are activated by endogenous glutamate; and activate a Na ϩ -Ca 2ϩ exchanger through G-protein, PLC, IP 3 , and Ca 2ϩ -calmodulin mechanisms to excite the cell, thus providing postsynaptic mechanisms to enhance or prolong baroreceptor signal transmission. I N T R O D U C T I O NThe nucleus tractus solitarius (NTS) is the principal brain stem site for coordinating CNS control of blood pressure. Second-order NTS neurons are the first site of synaptic contact of the primary baroreceptor afferent fibers, where the blood pressure-related sensory information is first subject to neuromodulation. When a change in blood pressure occurs, the information is rapidly and efficiently transmitted to the central baroreflex network by glutamate binding to ionotropic glutamate receptors on the second-order baroreceptor neurons in NTS (Aylwin et al. 1997; Ohta and Talman 1994; Talman 1989). At these synapses, the information is fine-tuned by presynaptic and postsynaptic influences originating from local networks and other brain regions so that the baroreceptor signal output to sympathetic and parasympathetic premotoneuronal pools is optimized to regulate blood pressure. Dysregulation of barore...

Differential Metabotropic Glutamate Receptor Expression and Modulation in Two Neocortical Inhibitory Networks

“…3) The differential mGluR modulation may serve as a mechanism of selective circuit activation during glutamate spillover because mGluRs are usually extrasynaptic and can only be activated during intense level of activation of excitatory inputs (Sekizawa and Bonham 2006). 4) Alternatively, if the ambient glutamate levels are altered during certain brain states (cf.…”

Regulation of Synaptic Transmission by Ambient Extracellular Glutamate

“…Indeed, both excitatory and inhibitory effects have been noted and attributed to tonic activation of mGluRs. For example, activation of excitatory sodium/calcium exchange in baroreceptors has been attributed to tonic activation of group I mGluRs (Sekizawa and Bonham 2006). Tonic activation of group III mGluRs causes suppression of supraoptic nucleus spontaneous activity and also inhibition of hypocretin/orexin neurons (Boudaba and others 2003;Acuna-Goycolea and others 2004).…”

Rapid Direct Excitation and Long-Lasting Enhancement of NMDA Response by Group I Metabotropic Glutamate Receptor Activation of Hypothalamic Melanin-Concentrating Hormone Neurons

“…First, to study the Na ϩ contribution to DHPG-induced depolarization in MCH neurons, we performed experiments in which NaCl was replaced by equimolar concentrations of Tris-HCl or choline chloride in the extracellular solution in the presence of TTX (Liu et al, 2002;Wu et al, 2004;Sekizawa and Bonham, 2006). When Na ϩ was replaced by Tris, the DHPG-induced depolarization was almost completely abolished in all of the cells tested ( Fig.…”