Modulation of a presynaptic hyperpolarization‐activated cationic current (I_h) at an excitatory synaptic terminal in the rat auditory brainstem

Abstract

A hyperpolarization‐activated non‐specific cation current, Ih, was examined in bushy cell bodies and their giant presynaptic terminals (calyx of Held). Whole‐cell patch clamp recordings were made using an in vitro brain slice preparation of the cochlear nucleus and the superior olivary complex. The aim was to characterise Ih in identified cell bodies and synaptic terminals, to examine modulation by presynaptic cAMP and to test for modulatory effects of Ih activation on synaptic transmission. Presynaptic Ih was activated by hyperpolarizing voltage‐steps, with half‐activation (V1/2) at –94 mV. Activation time constants were voltage dependent, showing an e‐fold acceleration for hyperpolarizations of –32 mV (time constant of 78 ms at –130 mV). The reversal potential of Ih was –29 mV. It was blocked by external perfusion of 1 mm CsCl but was unaffected by BaCl2. Application of internal cAMP shifted the activation curve to more positive potentials, giving a V1/2 of –74 mV; hence around half of the current was activated at resting membrane potentials. This shift in half‐activation was mimicked by external perfusion of a membrane‐permeant analogue, 8‐bromo‐cAMP. The bushy cell body Ih showed similar properties to those of the synaptic terminal; V1/2 was –94 mV and the reversal potential was –33 mV. Somatic Ih was blocked by CsCl (1 mm) and was partially sensitive to BaCl2. Somatic Ih current density increased with postnatal age from 5 to 16 days old, suggesting that Ih is functionally relevant during maturation of the auditory pathway. The function of Ih in regulating presynaptic excitability is subtle. Ih had little influence on EPSC amplitude at the calyx of Held, but may be associated with propagation of the action potential at branch points. Presynaptic Ih shares properties with both HCN1 and HCN2 recombinant channel subunits, in that it gates relatively rapidly and is modulated by internal cAMP.

Hyperpolarization-Activated Currents Regulate Excitability in Stellate Cells of the Mammalian Ventral Cochlear Nucleus

“…For the same voltage steps, slow was 190 ms in octopus, 960 ms in T stellate, and 560 ms in D stellate cells. Bushy cells express g h with characteristics generally similar to those described here for stellate neurons; measurements in bushy cells are not directly comparable because they were made from younger animals and at lower temperatures (Cuttle et al 2001); the expression and possibly the voltage dependence of I h are developmentally regulated in bushy cells as in other cell types (Cuttle et al 2001;Tanaka et al 2003).…”

“…In T and D stellate cells, 8-BrcAMP shifted its voltage dependence in the depolarizing direction. Increases in intracellular cAMP shift the voltage range of activation in the depolarizing direction with little or no change in g h max in many cell types including bushy cells (Banks et al 1993;Cathala and Paupardin-Tritsch 1999;Chen et al 2001;Cuttle et al 2001;DiFrancesco and Tortora 1991;Ingram and Williams 1996;Ludwig et al 1998;McCormick and Pape 1990b;Saitow and Konishi 2000;Santoro and Tibbs 1999;Santoro et al 1998;Tokimasa and Akasu 1990;Vargas and Lucero 1999). The maximal shift is related to the type of channels that form I h and also to the amount of basal modulation by the resting levels of cAMP (Chen et al 2001).…”

“…The remainder of the VCN contains intermingled bushy and stellate cells with bushy cells being more common anteriorly and stellate cells more common posteriorly. The low input resistances that result from the activation of g h and a low-voltage activated K ϩ conductance, g KL , make responses to synaptic currents in octopus and bushy cells fast and precisely timed, and responses to current pulses transient (Bal and Oertel 2000;Cuttle et al 2001;Manis and Marx 1991;Oertel et al 2000). The absence (or near absence) of g KL in stellate cells allows them to fire tonically when they are depolarized; their rates of firing are sensitive to small changes in resting currents (Ferragamo and Oertel 2002;Fujino and Oertel 2001;Oertel et al 1990).…”

Information processing in the axon

“…and at the calyx of Held 28 . I h is an inward cationic current that is slowly activated by hyperpolarization.…”

Physiology of long pranayamic breathing: Neural respiratory elements may provide a mechanism that explains how slow deep breathing shifts the autonomic nervous system

“…Inhibitory current regulates excitability of nervous tissues [41] and is known to elicit synchronization of neural elements which typically is indicative of a state of relaxation [42]. Synchronization within the hypothalamus and the brainstem [43] is likely responsible for inducing the parasympathetic response [44] Figure 1 Diagram of the series of events that occur during the autonomic shift present in pranayamic slow breathing.…”