title: In vivo 4-aminopyridine treatment alters the neurotoxin 3-acetylpyridine-induced  plastic changes in intrinsic electrophysiological properties of rat  cerebellar  Purkinje neurones.
abstract: Electrophysiological dysfunction of Purkinje cells causes cerebellar ataxia. Recent studies indicated that 4-aminopyridine (4-AP) can prevent the attacks in patients with episodic ataxia type 2. However, the cellular mechanism(s) by which 4-AP might be beneficial for the improvement of motor function remain unclear. Here, electrophysiological and behavioural consequences of in vivo co-treatment with 4-AP against 3-acetylpyridine (3-AP)-induced ataxia in rats were assessed. Combined treatment with 4-AP partially improved motor behaviour compared to the ataxic rats. Treatment with 3-AP alone induced plastic alterations in the cells' intrinsic properties, so that the latency of the initial neural spike was significantly increased (Pb 0.001); however, both instantaneous firing frequency and amplitude of calcium spikes were significantly (Pb 0.001) suppressed. 3-AP treatment also resulted in significant decrease in the duration of action potential (Pb 0.05) and the amplitude of afterhyperpolarization ((Pb 0.05) as well as post-stimulus hyperpolarization potentials (Pb 0.001). Purkinje cells in rats co-treated with 4-AP, however, fired predominantly in rhythmic bursts. The mean amplitude of Ca2+ spikes was significantly (Pb 0.001) greater compared to ataxic rats, but similar to control value. As evidenced by a significant decrease (Pb 0.001) in the first spike latency, the cells' intrinsic excitability was also increased. In 4-AP co-treated group, the duration of action potential was also significantly lengthened (Pb 0.001) compared to control and 3-AP group. These results suggest that modulation of intrinsic electrical properties and potentiation of Ca2+ channels function caused by in vivo 4-AP treatment is likely to be partly responsible for its neuroprotective action.
authors.affiliation: Neuroscience Research Centre and Department of Physiology, Medical School, Shahid Beheshti Medical Sciences University, Evin, Tehran, Iran.
authors.forename: Iran
authors.initials: I
authors.lastname: Goudarzi
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Kaffashian
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shabani
authors.forename: Hashem
authors.initials: H
authors.lastname: Haghdoost-Yazdi
authors.forename: Gila
authors.initials: G
authors.lastname: Behzadi
authors.forename: Mahyar
authors.initials: M
authors.lastname: Janahmadi
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D001259:Ataxia / Q000473:pathology / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects; D004347:Drug Interactions; D055724:Electrophysiological Phenomena / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009498:Neurotoxins / Q000633:toxicity*; D011689:Purkinje Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats
chemical_list: D009498:Neurotoxins; D011725:Pyridines; C010835:3-acetylpyridine; D015761:4-Aminopyridine