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

• Published in: The Journal of physiology 2001-08, Vol.534 (3), p.733-744
• Main Authors: Cuttle, Matthew F., Rusznák, Zoltán, Wong, Adrian Y. C., Owens, Steven, Forsythe, Ian D.
• Format: Article
• Language: English
• Subjects: Animals; Auditory Pathways - physiology; Brain Stem - physiology; Cations - metabolism; Electrophysiology; In Vitro Techniques; Ion Channels - physiology; Nerve Endings - physiology; Original; Presynaptic Terminals - physiology; Rats; Rats, Inbred Strains; Synapses - physiology; Synaptic Transmission - physiology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1111/j.1469-7793.2001.00733.x

A hyperpolarization-activated non-specific cation current, I h , 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 I h in identified cell bodies and synaptic terminals, to examine modulation by presynaptic cAMP and to test for modulatory effects of I h activation on synaptic transmission. Presynaptic I h was activated by hyperpolarizing voltage-steps, with half-activation ( V 1/2 ) 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 I h was –29 mV. It was blocked by external perfusion of 1 m m CsCl but was unaffected by BaCl 2 . Application of internal cAMP shifted the activation curve to more positive potentials, giving a V 1/2 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 I h showed similar properties to those of the synaptic terminal; V 1/2 was –94 mV and the reversal potential was –33 mV. Somatic I h was blocked by CsCl (1 m m ) and was partially sensitive to BaCl 2 . Somatic I h current density increased with postnatal age from 5 to 16 days old, suggesting that I h is functionally relevant during maturation of the auditory pathway. The function of I h in regulating presynaptic excitability is subtle. I h 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 I h shares properties with both HCN1 and HCN2 recombinant channel subunits, in that it gates relatively rapidly and is modulated by internal cAMP.