Modulation of a presynaptic hyperpolarization-activated cationic current (I(h)) at an excitatory synaptic terminal in...

1. 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. 2. 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 mM CsCl but was unaffected by BaCl(2). 3. 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. 4. 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 mM) 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. 5. 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.