Somatic vs. dendritic responses to hypercapnia in chemosensitive locus coeruleus neurons from neonatal rats

Abstract

Cardiorespiratory control is mediated in part by central chemosensitive neurons that respond to increased CO2 (hypercapnia). Activation of these neurons is thought to involve hypercapnia-induced decreases in intracellular pH (pHi). All previous measurements of hypercapnia-induced pHi changes in chemosensitive neurons have been obtained from the soma, but chemosensitive signaling could be initiated in the dendrites of these neurons. In this study, membrane potential ( Vm) and pHi were measured simultaneously in chemosensitive locus coeruleus (LC) neurons from neonatal rat brain stem slices using whole cell pipettes and the pH-sensitive fluorescent dye pyranine. We measured pHi from the soma as well as from primary dendrites to a distance 160 μm from the edge of the soma. Hypercapnia [15% CO2, external pH (pHo) 7.00; control, 5% CO2, pHo 7.45] resulted in an acidification of similar magnitude in dendrites and soma (∼0.26 pH unit), but acidification was faster in the more distal regions of the dendrites. Neither the dendrites nor the soma exhibited pHi recovery during hypercapnia-induced acidification; but both regions contained pH-regulating transporters, because they exhibited pHi recovery from an NH4Cl prepulse-induced acidification (at constant pHo 7.45). Exposure of a portion of the dendrites to hypercapnic solution did not increase the firing rate, but exposing the soma to hypercapnic solution resulted in a near-maximal increase in firing rate. These data show that while the pHi response to hypercapnia is similar in the dendrites and soma, somatic exposure to hypercapnia plays a major role in the activation of chemosensitive LC neurons from neonatal rats.