My understanding of direct vs indirect is that in the presence of TTX you can only measure activity at the synapse. However, I was discussing this with a colleague that thought it was only able to measure a postsynaptic effect. My thought is if you record in current clamp in the presence of TTX and apply a drug, if it releases a huge amount of neurotransmitter- such as glutamate- you could still get a depolarization of the post-synaptic membrane through the large influx of synaptic calcium. Is this wrong to believe?
Hi Brandon,
TTX is a sodium channel blocker and in neurons it blocks the production of action potentials, and thus its propagation too. It is possible, however, to record synaptic activity I the presence of TTX (e.g mEPSC). Following your example, you could just add KCl to your bath solution and that would depolarize the cell, if the depolarization is big enough that you activate CaV1.2 in the presinaptic terminal, the influx of calcium could produce the release of neurotransmitter which would produce postsynaptic depolarization, however that would not trigger an action potential since the sodium channels responsible for the initiation of the action potentials would be blocked. The KCl treatment could in itself also depolarize the postsynaptic terminal and that could lead to calcium entry. In some cells, such as pituitary secretory cells, action potentials are not sodium driven but calcium driven so in that situation the effects of TTX would be totally different.
Hope this helps,
Ezequiel
J agree to the answer of Fernandez. TTX block voltage gated sodium channels. Action potentials in nerve cells, as I know, only by voltage gated sodium channels. Pace maker cells channels can be excited only until the firing level by the enter of Ca ion, but to make action potentials it still needs voltage gated sodium channels.
Hi Brandon,
Excitatory (AMPAR- and NMDAR-mediated) synaptic input is known to result in dendritic regenerative potentials mediated by Ca2+ -- so-called Ca2+ spikes -- in the presence of 1 uM TTX (for example, in layer 5 pyramidal neurons, see Schiller et al, 1994, J Physiol, Larkum et al, 1999, PNAS). These Ca2+ potentials tend to be isolated to the dendritic branch where synaptic input has been activated, do not always propagate to the soma, and usually do not invade other dendrit ic branches (see e.g., Cai et al, 2004, Neuron). Therefore you are right in assuming that given enough synaptic activation the postsynaptic mebrane can be depolarized through Ca2+ electrogenesis, even when Na+ channels are blocked.
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