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

1. A hypepolarization-activated non-specific cation current, I-h was examin ed in bushy cell bodies and their giant presynaptic terminals (calyx of Hel d). Whole-cell patch clamp recordings were made using an ire vitro brain sl ice preparation of the cochlear nucleus and the superior olivary complex. T he aim was to characterise I-h in identified cell bodies and synaptic termi nals, 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 Hal f-activation (V-1/2) at -94 mV. Activation time constants were voltage depe ndent, showing an e-fold acceleration for hyperpolarizations of -32 mV (tim e constant of 78 ms at -130 mV). The reversal potential of I-h was -29 mV. It was blocked by external perfusion of 1 nm CsCl but was unaffected by BaC l2. 3. Application of internal cAMP shifted the activation curve to more Positi ve potentials, giving a V-1/2 of -74 mV; hence around half of the current w as activated at resting membrane potentials. This shift in half-activation was mimicked by external perfusion of a membrane-permeant analogue, 8-bomo- cAMP. 4. The bushy cell body I-h showed similar properties to those of the synapt ic terminal; V-1/2 was -94 mV and the reversal potential was -33 mV. Somati c I-h was blocked by CsCl (1 mM) and was partially sensitive to BaCl2. Soma tic 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 aud itory 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. Pres ynaptic I-h shares properties with both HCN1 and HCN2 recombinant channel s ubunits, in that it gates relatively rapidly and is modulated by internal C AMP.