Interaction between bradykinin and voltage-sensitive sodium channels in myelinated nerve fibers

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Abstract
The effects of externally and internally applied bradykinin on the excitability of single myelinated nerve fibers were studied. External bradykinin (10 μM) slightly prolongs the action potential of a single myelinated nerve fiber; hence, when the fibers are stimulated by long-lasting pulses, this raises the frequency of repetitive firing in sensory fibers and evokes repetitive activity in motor fibers. Under voltage-clamp conditions, sodium channel inactivation is slowed, while sodium channel activation remains unaffected. Prolonged depolarization of th membrane leads to a maintained sodium current. The voltage dependence of the steady-state sodium current inactivation (h ∞) is shifted in the depolarized direction by ∼ 10 mV. Internally applied bradykinin produces a frequency-dependent block of the sodium current. The phenomena described here imply that more than one site on the sodium channel is modified by bradykinin.