Hyperpolarization-activated currents in neurons of the rat basolateral amygdala

Abstract

1. A single microelectrode was used to obtain current-clamp or voltage-clamp recordings from two neuronal cell types (pyramidal and late-firing neurons) in the basolateral nucleus of the amygdala (BLA) in slices of the rat ventral forebrain. Conductances activated by hyperpolarizing voltage steps from a holding potential of -70 mV were identified and their sensitivity to muscarinic modulation was determined using bath superfusion of carbachol. 2. Unclamped pyramidal neurons exhibited anomalous rectification, seen as a slowly developing depolarizing sag in the electronic potential in response to a hyperpolarizing current pulse. 3. Stepping voltage-clamped pyramidal neurons to command potentials of between -70 and -100 mV activated a slowly developing inward current (ISlow) that followed a single exponential time course. Larger hyperpolarizing voltage steps evoked a rapidly developing inward current (IFast) that preceded the development of ISlow. 4. The ISlow component reversed at a level positive to the -70 mV holding potential. Its rate of activation accelerated as the hyperpolarizing voltage step was made more negative. The threshold for activation of the conductance underlying ISlow was approximately -60 mV, with half-activation occurring at -90 mV. 5. Extracellular Cs+ (2 mM) blocked ISlow and eliminated anomalous rectification in unclamped pyramidal neurons. The inhibition of ISlow by Cs+ was also associated with membrane hyperpolarization and reduction of the medium afterhyperpolarization. ISlow was unaffected by extracellular Ba2+ (100 microM). The properties of this current appeared similar to that of the mixed cationic H-current previously identified in other neurons. 6. In comparison with pyramidal cells, unclamped late-firing neurons displayed a lesser but more rapidly developing anomalous rectification in response to large hyperpolarizations from rest. In voltage clamp, hyperpolarizing steps to command potentials more negative than -100 mV elicited IFast. Late-firing neurons expressed little or no ISlow. 7. The properties of IFast were identical in both pyramidal and late-firing neurons. This current reversed at a potential negative to -70 mV. Its rate of current activation increased with the magnitude of the hyperpolarizing voltage step. This rate was approximately sevenfold faster than ISlow activation recorded at the same membrane potential. IFast was blocked by 2 mM extracellular Cs+ and reduced by 100 microM extracellular Ba2+. The threshold for activation of the underlying conductance was approximately -85 mV, with half-activation occurring at -112 mV. The properties of IFast were similar to those of the inward rectifier current previously identified in other central neurons. 8. Carbachol (40 microM) largely blocked IFast without affecting its rate of activation.(ABSTRACT TRUNCATED AT 400 WORDS)

NPY Y1 Receptors Differentially Modulate GABAA and NMDA Receptors via Divergent Signal-Transduction Pathways to Reduce Excitability of Amygdala Neurons

“…In response to depolarizing current injection of increasing amplitude, neurons initially fired either a single action potential or a doublet/triplet burst, after which a slower, more rhythmic firing pattern was observed (Figure1a, top). These neurons also showed a depolarizing sag in the voltage excursion in response to hyperpolarizing current pulses (Figure1a, bottom) (Womble and Moises, 1993). Initially, using current-clamp mode, we showed that bath pretreatment with L-P NPY (200 or 400 nM) induced a significant increase of evoked inhibitory postsynaptic potentials (eIPSPs) (RM-ANOVA 200 nM L-P NPY: F (2,18) ¼ 5.13, P ¼ 0.017; 400 nM L-P NPY: F (2,18) ¼ 5.8, P ¼ 0.011; Figure 1b), which differed significantly from baseline during both 200 and 400 nM drug application (P ¼ 0.01 and 0.01, respectively, Dunnett's) and remained significantly increased from baseline during wash for 400 nM dose (P ¼ 0.02, Dunnett's; Figure 1b).…”

Hyperpolarization‐activated cationic currents (Ih) in neurones of the trigeminal mesencephalic nucleus of the rat

“…However, in other neurones Ih can contribute substantially to the resting and active properties of neurones, e.g. thalamic relay neurones (McCormick & Pape, 1990), hippocampal neurones (Maccaferri et al 1993;Gasparini & DiFrancesco, 1997), neurones of the basolateral amygdala (Womble & Moises, 1993) and ventrobasal thalamic neurones (Williams et al 1997). The reasons why Ih is active at rest in some neurone types and not in others is unclear at present.…”

“…Pharmacologically, Ih can be discriminated from other hyperpolarization-activated currents such as inward rectifier potassium currents because it is not blocked by intracellular Cs¤ or extracellular Ba¥ (Womble & Moises, 1993). The use of the bradycardiac agent ZD7288, developed as an inhibitor of If (the cardiac hyperpolarization-activated cation current), provides further pharmacological evidence that Ih is the neuronal equivalent of If.…”

Hyperpolarization-Activated Cation Channels: From Genes to Function

“…Speculations on the nature of I INS reach from models where this current represents a leak conductance or an experimental artifact to models in which I INS is caused by a second pore that is found within the same HCN channel that produces I SS or a second channel population associated with HCN channels (236,237,312). Depending on the cell type, the activation of I SS can be empirically described by either a single (120,136,200,261,264,355,393,425) or double exponential function (17,104,131,175,248,402). As mentioned above, kinetics of I SS are quite variable (111,118).…”