Tertiapin

A voltage-dependent blockade by intracellular cations at voltages more positive than the K+ reversal potential is the mechanism underlying this feature.

[6] GIRK1 and -4 are subunits of the muscarinic potassium channels (KACh) and have an important role in the slowing down of the heart rate in response to parasympathetic stimulation via acetylcholine.

An inhibition will result in loss of potassium, as observed in Bartter syndrome, which can be caused by mutations in the ROMK channels.

The block of BK cells is voltage-, concentration- and use-dependent, meaning the blockage changes with different stimulation voltages and frequencies, different concentrations and with the duration of application of tertiapin.

Total blockage by tertiapin prolongs the duration of the action potential and inhibits the afterhyperpolarization amplitude, leading to an increase of the neuronal excitability.

Eventually this will lead to inactivation of the voltage-gated Na+ channels of the dorsal root ganglion neurons, reducing sensory transmission to the central nervous system.

[9] Excessive stimulation with acetylcholine can induce an AV-block in the heart as shown in guinea pigs, which can be prevented by blockage of the KAch channels by tertiapin.