Interleukin-1, corticotropin-releasing factor and resistant calcium currents in amygdala neurons

Interleukin-1{dollar}beta{dollar} (IL-1{dollar}beta{dollar}), corticotrophin-releasing factor (CRF), and the amygdala are involved in regulating stress responses and IL-1{dollar}beta{dollar} and CRF receptors are located in amygdala. We investigated the mechanisms of action of IL-1{dollar}beta{dollar} and CRF in amygdala neurons using intracellular recording and whole-cell patch-clamp methodology. Also analyzed in this study were the electrophysiology and pharmacology of multiple types of whole-cell Ca{dollar}sp{lcub}2+{rcub}{dollar} currents (I{dollar}rmsb{lcub}Ca{rcub}{dollar}) in neurons of the central amygdala (CeA).; In the basolateral amygdala (BLA), IL-1{dollar}beta{dollar} is primarily inhibitory. IL-1{dollar}beta{dollar} hyperpolarizes the membrane and decreases input resistance. The hyperpolarization persists in tetrodotoxin, has reversal potentials of {dollar}-{dollar}74 mV and {dollar}-{dollar}40 mV with Kacetate and KCl electrodes, respectively, and is not observed in the presence of bicuculline or in acutely dissociated BLA neurons, suggesting that the hyperpolarization involves a chloride conductance which is mediated indirectly through enhancement of endogenous GABA. IL-1{dollar}beta{dollar} also inhibits synaptic potentials but does not depress responses to glutamate receptor or GABA receptor agonists in either brain slices or acutely dissociated BLA neurons, suggesting that the inhibition is presynaptic, possibly mediated by depressing calcium currents.; High-voltage activated calcium currents in neurons isolated from CeA are composed of at least four distinct components reflecting dihydropyridine (DHP)- and neurotoxin-sensitive and -insensitive currents. The resistant current in CeA neurons comprises the largest component (37-53%) of I{dollar}rmsb{lcub}Ca{rcub}{dollar}, while the remainder is composed of L- (22%), N- (30%), Q-type (12%) Ca{dollar}sp{lcub}2+{rcub}{dollar} currents. L-type Ca{dollar}sp{lcub}2+{rcub}{dollar} currents are recorded in only 70% while P-type Ca{dollar}sp{lcub}2+{rcub}{dollar} current is not present in CeA neurons. Furthermore, the resistant currents have electrophysiological and pharmacological similarities to R-type and {dollar}alpharmsb{lcub}1E{rcub}{dollar} Ca{dollar}sp{lcub}2+{rcub}{dollar} currents, suggesting that the DHP- and neurotoxin-resistant channels in CeA neurons are composed of {dollar}alpharmsb{lcub}1E{rcub}{dollar} subunits.; CRF increases the I{dollar}rmsb{lcub}Ca{rcub}{dollar} which is resistant to DHPs and neurotoxins in CeA neurons. This effect is concentration-dependent (EC{dollar}sb{lcub}50{rcub}{dollar} = 15.6 nM), not accompanied by shifting the voltage dependence of steady-state activation or inactivation of the I{dollar}rmsb{lcub}ca{rcub}{dollar}, and mediated through a receptor mechanism since the effect is blocked by CRF receptor antagonist, {dollar}alpha{dollar}-helical CRF{dollar}sb{lcub}9-41{rcub}{dollar}. These studies suggest that in CeA neurons CRF increases a calcium current mediated through {dollar}alpharmsb{lcub}1E{rcub}{dollar} channels, and this effect and the effects of IL-1{dollar}beta{dollar} may be functionally relevant in regulating autonomic, endocrine and behavioral responses to stress.