Bradykinin effect on conduction of rhythmic series of pulses through the neuromuscular synapse

Abstract

Bradykinin did not change the amplitude and duration of growth and decrease of individual currents of the terminal plate, but potentiated the depression of amplitudes of consecutive currents during stimulation of the motor nerve at a frequency of 10-60 Hz under conditions of two-electrode fixation of potential on a frog neuromuscular preparation. The origin of this effect is presynaptic, because it does not depend on the activity of acetylcholinesterase and is associated with a longer increase in the terminal plate currents which are synchronous with the amplitude depression. The deconvolution method revealed a slower kinetics of the mediator secretion under the effect of bradykinin. Bradykinin impairs the conduction of rhythmic pulse series through the synapse by augmenting the asynchronism of the transmitter quantum secretion from the motor nerve endings, which may underlie the development of muscular asthenia observed in inflammatory and allergic reactions.Key Words: synapse; plasticity; bradykinin; secretion; acetylcholine Bradykinin (BK) is a humeral factor whose concentration increases in damaged tissues and during allergic and inflammatory reactions [12]. BK effects on smooth muscular cells and sympathetic neurons, which it activates through the second messengers diacylglycerol and inositol trisphosphate with subsequent increase in the concentration of intracellular calcium, are studied in detail [4]. There are no published data on the effect of BK on the peripheral neuromuscular system; experiments in a cell culture of the glioma synaptically connected to the skeletal muscular fibers revealed an inhibitory effect of this agent on synaptie transfer because of suppressed acetylcholino (AC) secretion [13]. If a similar effect of BK develops in the neuromuscular system in rive, it may lead to myasthenia in inflammatory and allergic diseases. Therefore we investigated the effect of BK on the amplitude and time course of currents in the terminal plate (TPC) during rhythmic stiDepartment of Normal Physiology, Kazan State Medical University mutation of the motor nerve under conditions of intact high (close to the normal)level of induced secretion of AC. MATERIALS AND METHODSExperiments were carried out on a neuromuscular sciatic nerve--musculus sartorius preparation of Rana temporaria at 20-21~ The muscle was perfused with Ringer's solution containing (in mmolfliter): 115 NaCI, 2.5 KC1, 1.8 CaC 89 and 2.4 NaHCO v pH 7.3. In order to preserve induced secretion of the mediator at the level close to the normal, muscular contractions were blocked by transverse section of the muscle. TPC were recorded using two-electrode fixation of the membrane potential with a numbering of 5-20 i~see/point. The TPC parameters were calculated on a PC. The time course of secretion during a single synaptic transfer was evaluated by the deconvolution method [8,14]. The methods were described in detail previously [1][2][3].