Abstract
Some of the excitatory effects of norepinephrine on central neurons are mediated by alpha-1 (α1) adrenoceptors. These receptors are coupled to the Gq family of G proteins, and hence stimulate hydrolysis of the membrane phospholipid phosphatidylinositol-4,5-bisphosphate. Other receptors of this type can excite neurons by inhibiting the subthreshold voltage-gated potassium M-current. We tested this possibility using rat sympathetic neurons transformed to express α1a receptors. The α1 agonist phenylephrine strongly inhibited the M-current recorded under voltage-clamp by 72 ± 11 % (n = 4) and in an unclamped neuron dramatically increased the number of action potentials produced by a 2 s depolarizing current step from 2 to 40, without effect on control neurons devoid of α1 receptors. We suggest that this might be a potential cause of the increased excitability produced by norepinephrine in some central neurons.
Highlights
Alpha-1 (a1) adrenoceptors are widely distributed in the central nervous system (Jones et al 1985; Day et al 1997)
Some of the excitatory effects of norepinephrine on central neurons are mediated by alpha-1 (a1) adrenoceptors
The a1 agonist phenylephrine strongly inhibited the M-current recorded under voltageclamp by 72 ± 11 % (n = 4) and in an unclamped neuron dramatically increased the number of action potentials produced by a 2 s depolarizing current step from 2 to 40, without effect on control neurons devoid of a1 receptors
Summary
Alpha-1 (a1) adrenoceptors are widely distributed in the central nervous system (Jones et al 1985; Day et al 1997) There they mediate some of the effects of norepinephrine, including a membrane depolarization and enhanced action potential firing (e.g., supra-optic nucleus: Ogata and Matsuo 1986; cultured spinal neurons: Legendre et al.1988; cerebral cortex and thalamus: McCormick et al 1991; lateral geniculate nucleus: McCormick 1992). These receptors are G protein-coupled receptors (GPCRs) that link primarily to the Gq family of G proteins and thereby stimulate hydrolysis of the membrane phospholipid phosphatidylinositol-4,5-bisphosphate (PIP2) (Hawrylyshyn et al 2004). This may be because most of the cells studied so far did not possess prominent M-currents, or perhaps because the current is not very responsive to a1 receptor stimulation (though tests on peripheral parasympathetic neurons suggest otherwise: Shibata and Taketani 2001)
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