Inhibitory postsynaptic

An inhibitory postsynaptic potential is a local hypetpo-larizing potential at a postsynaptic membrane, which is elicited by the release of an inhibitory neurotransmitter via an inhibitory postsynaptic current. 

The GABAA-receptor and the glycine receptor are Cl-channels (Table 1). When they open at a resting membrane potential of about -60 mV, the consequence is an entry of Cl-, hyperpolarization and an inhibitory postsynaptic potential (DPSP Fig. 1). 

An inhibitory input increases the influx of Cl to make the inside of the neuron more negative. This hyperpolarisation, the inhibitory postsynaptic potential (IPSP), takes the membrane potential further away from threshold and firing. It is the mirror-image of the EPSP and will reduce the chance of an EPSP reaching threshold voltage. 

Figure 1.4 Ionic basis for excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs). Resting membrane potential ( — 70 mV) is maintained by Na+ influx and K+ efflux. Varying degrees of depolarisation, shown by different sized EPSPs (a and b), are caused by increasing influx of Na. When the membrane potential moves towards threshold potential (60-65 mV) an action potential is initiated (c). The IPSPs (a b ) are produced by an influx of Cl. Coincidence of an EPSP (b) and IPSP (a ) reduces the size of the EPSP (d)...

Figure 11.5 Chloride distribution and the GABAa response. The change in membrane voltage (Fm) that results from an increase in chloride conductance following activation of GABAa receptors is determined by the resting membrane potential and the chloride equilibrium potential (Fci)- (a) Immature neurons accumulate CF via NKCC, while mature neurons possess a Cl -extruding transporter (KCC2). (b) In immature neurons GABAa receptor activation leads to CF exit and membrane depolarisation while in mature neurons the principal response is CF entry and h5q)erpolarisation. This is the classic inhibitory postsynaptic potential (IPSP)...

There have been a number of observations which show increased excitation and/or reduced inhibition in slices prepared from human epileptic brain tissue. Thus burst discharges can be evoked with stimuli that would not do so in normal animal tissue and these can be blocked by NMD A receptor antagonists. The inhibitory postsynaptic currents (IPSCs) in hippocampal dentate granule cells in slices prepared from temporal lobe epileptic tissue are in fact reduced by stimulation that activates NMDA currents (Isokawa 1996), which are more prolonged than usual and show changes in slope conductance. 

Figure 5.3 Spatial summation. Multiple excitatory postsynaptic potentials (EPSPs) or inhibitory postsynaptic potentials (IPSPs) produced by many presynaptic neurons simultaneously may add together to alter the membrane potential of the postsynaptic neuron. Sufficient excitatory input (A and B) will depolarize the membrane to threshold and generate an action potential. The simultaneous arrival of excitatory and inhibitory inputs (A and C) may cancel each other out so that the membrane potential does not change.

In addition to direct enhancement of channel activity, PTKs can indirectly increase GABA-evoked inhibitory current by recruiting intracellular GABAaR to the surface of postsynaptic membrane. Insulin has been shown to increase surface expression GABAaR in transfected human embryonic kidney cells. In central neurons insulin rapidly increases the expression of functional postsynaptic GABAaR in a tyrosine kinase-dependent manner, resulting in an increase in the amplitude of the miniature inhibitory postsynaptic currents. 

In addition to the excitatory effects described above, there is some evidence that administration of hallucinogens can depress MSRs and PSRs in intact animals. These depressant effects, however, do not appear to be simply mediated by stimulation of inhibitory postsynaptic 5-HT receptors in the spinal cord, since they are blocked by 5-HT antagonists. 

Some of the depressant behavioral effects of hallucinogens may involve inhibitory postsynaptic 5-HT receptors. For example, depressant effects of hallucinogens on startle and locomotor activity may result from activation of these receptors, since 5-HT itself has similar effects. Studies on supersensitivity are lacking, however, and, again, the absence of selective antagonists prevents definitive conclusions. 

HD HIV HMG hpp IL-2 IPSP hydroxydanaidal human immunodeficiency virus hydroxymethylglutaryl hours postparasitization interleukin 2 inhibitory postsynaptic potential... 

Activation of ionotropic mechanisms creates postsynaptic potentials. An influx of cations or efflux of anions depolarizes the neuron, creating an excitatory-postsynaptic potential (EPSP). Conversely, an influx of anions or efflux of cations hyperpolarizes the neuron, creating an inhibitory-postsynaptic potential (IPSP). Postsynaptic potentials are summated both... 

When receptors are directly linked to ion channels, fast excitatory postsynaptic potentials (EPSPs) or inhibitory postsynaptic potentials (IPSPs) occur. However, it is well established that slow potential changes also occur and that such changes are due to the receptor being linked to the ion channel indirectly via a second messenger system. 

Fiorillo CD, Williams JT (1998) Glutamate mediates an inhibitory postsynaptic potential in dopamine neurons. Nature 394 78-82... 

Interaction of excitatory and inhibitory synapses. On the left, a suprathreshold stimulus is given to an excitatory pathway (E) and an action potential is evoked. On the right, this same stimulus is given shortly after activating an inhibitory pathway (I), which results in an inhibitory postsynaptic potential (IPSP) that prevents the excitatory potential from reaching threshold. 

D2 bromocriptine Phenothiazines, butyrophenones Inhibitory (presynaptic) i Ca2+ Inhibitory (postsynaptic) t in K+ conductance, cAMP... 

GABA receptors are divided into two main types GABAa and GABAB. inhibitory postsynaptic potentials in many areas of the brain have a fast and slow component. The fast component is mediated by GABAa receptors and the slow component by GABAB receptors. The difference in kinetics stems from the differences in coupling of the receptors to ion channels. GABAa... 

---