Modifications of synaptic efficacy play a crucial role in information processing in the brain. In particular, they are thought to be very important for the refinement of neural circuitry, information storage, learning and memory. Therefore, investigating the mechanisms that modulate synaptic transmission is of fundamental importance for understanding brain functions. In the present study, patch-clamp recordings were performed in order to investigate synaptic transmission in the hippocampus, focusing on a particular presynaptic mechanism that may affect synaptic efficacy. In particular we have explored the possibility that a particular type of calcium-dependent potassium channel, the BK channel, may affect the probability of transmitter release modifying the shape of the action potential at nerve terminals. BK channels are large conductance calcium- and voltage-activated potassium channels whose characteristic is to reduce cell excitability by increasing the open probability following elevation of intracellular calcium. BK channels targeted to active zones in presynaptic nerve terminals would limit calcium entry and transmitter release by reducing the duration of the presynaptic spike. While it has been demonstrated that BK channels regulate secretion and transmitter release at neurosecretory nerve terminals and at the neuromuscular junction, their functional role in central neurones is still uncertain. In the hippocampus BK channels would act as an “emergency brake” that would control transmitter release only under conditions of excessive depolarisation and accumulation of intracellular calcium. Here we show that, under basal experimental conditions, the selective BK channel blockers paxilline and iberiotoxin increase the frequency of spontaneously occurring EPSCS in the CA3 hippocampal region. These drugs did not affect miniature currents suggesting that their action was dependent on action potential firing. Moreover, at hippocampal CA3-CAB connections paxilline enhanced the probability of transmitter release in target cells by broadening the presynaptic spike. In particular, in the presence of paxilline an increase in successes rate and EPSC amplitude, and a concomitant decrease in paired pulse ratio were observed. BK channel blockers produced also a delayed release, particularly in response to the second action potential following with 50 ms delay the first one in paired pulses. These results are consistent with the hypothesis that BK channels are powerful modulators of transmitter release and synaptic efficacy in central neurones under normal conditions.
|Titolo:||BK channels control glutamate release at CA3-CA3 synapses in the rat hippocampus|
|Data di pubblicazione:||lug-2003|
|Appare nelle tipologie:||8.2 Magister thesis - Magister philosophiae|