2009 issue 3-4


Volume 25, issue 3-4

Review article

Two faces of GABA: inhibition and excitation

Wojciech Kostowski1, Anna Witanowska2
1. Zakład Farmakologii i Fizjologii Układu Nerwowego Instytutu Psychiatrii i Neurologii w Warszawie
2. Zakład Patofizjologii Warszawskiego Uniwersytetu Medycznego
Farmakoterapia w Psychiatrii i Neurologii, 2009, 3-4, 173–178
Keywords: GABA, inhibition, excitation, neurogenesis, epilepsy


GABA (γ-aminoburytic acid) is the primary inhibitory neurotransmitter in the adult brain. It regulated neuronal activity through hyperpolarization of the membrane potential . However, during early postnatal period, GABAergic transmission is excitatory. The nature of GABAergic neurotransmission is determined by the electrochemical gradient for Cl- , which depends on extra- and intracellular concentrations of chloride. During the postnatal period GABAergic transmission undergo from being excitatory to inhibitory. The switch of GABAergic responses is due to changes in expression of K+ -coupled Cl- transporter (KCC2 cotransporter).
Excitatory GABA action (i.e. membrane depolarization) is essential for morphological maturation of neurons in immature animals. GABA regulates also synaptic integration of newly generated neurons in the adult brain.
GABA-induced excitation plays also a role in mechanism of epilepsy. Interneurons producing GABA together with aberrantly behaving population of pyramidal neurons in the hippocampus can precipitate epileptic seizures. The findings showing that GABA in some instances can be ictogenic may explain why some antiepileptic GABA-promoting drugs, have occasionally been reported to be proconvulsant in clinical cases.
Further, GABA is able to induce depolarization in injured neurons thus leading to neuronal Ca2+ - dependent excitotoxicity.
GABA has also been found to evoke hormone release from neuroendocrine cells.
GABA-A receptor are expressed upon neuroendocrine cells such as insulin-secreting pancreatic β-cells and catecholamine-releasing adrenal chromaffin cells.
Thus, GABA can no longer be simply viewed as and inhibitory neurotransmitter which causes hyperpolarization of neuronal cells. The pharmacological and clinical consequences of excitatory properties of GABA seem to be of great importance.

Address for correspondence:
Zakład Farmakologii i Fizjologii Układu Nerwowego
Instytut Psychiatrii i Neurologii
ul. Sobieskiego 9, 02-957 Warszawa
tel 22 4582624, fax 22 8427644
e-mail: kostowsk@ipin.edu.pl