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The Journal of Neuroscience, September 29, 2004, 24(39):8416-8427; doi:10.1523/JNEUROSCI.1677-04.2004

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Cellular/Molecular
Facilitation of L-Type Ca²⁺ Channels in Dendritic Spines by Activation of ₂ Adrenergic Receptors

Tycho M. Hoogland and Peter Saggau

Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030

We studied the contribution of L-type Ca²⁺ channels to action potential-evoked Ca²⁺ influx in dendritic spines of CA1 pyramidal neurons and the modulation of these channels by the ₂ adrenergic receptor. Backpropagating action potentials (bAPs) (three at 50 Hz) were evoked by brief somatic current injections, and Ca²⁺ transients were recorded in proximal basal dendrites and associated spines. The R- and T-type Ca²⁺ channel blocker NiCl₂ (100 µM) significantly reduced Ca²⁺ transients in both spines and their parent dendrites (50%), suggesting that these channels are the major source of bAP-evoked Ca²⁺ influx in these structures. The L-type Ca²⁺ channel blockers nimodipine and nifedipine (both 10 µM) reduced spine Ca²⁺ transients by 10%, whereas the L-type Ca²⁺ channel activators FPL 64176 (2,5-dimethyl-4-[2-(phenylmethyl)benzoyl]-1H-pyrrole-3-carboxylic acid methylester) and Bay K 8644 ((±)-1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)-phenyl]-3-pyridine carboxylic acid methyl ester) (both 10 µM) significantly enhanced the spine Ca²⁺ transients by 40-50%. Activation of ₂ adrenergic receptors with salbutamol (40 µM) or formoterol (5 µM) resulted in significant enhancements of the spine (40-50%) but not dendritic Ca²⁺ transients. This increase was prevented when L-type Ca²⁺ channels were blocked with nimodipine (10 µM) or when cAMP-dependent protein kinase A (PKA) was inhibited with KT5720 (3 µM), Rp-cAMPS (Rp-adenosine cyclic 3',5'-phosphorothioate) (100 µM), or PKI (100 µM). The above data suggest that L-type Ca²⁺ channels are functionally present in dendritic spines of CA1 pyramidal neurons, contribute to spine Ca²⁺ influx, and can be modulated by the ₂ adrenergic receptor through PKA in a highly compartmentalized manner.

Key words: dendritic spine; CA1; calcium; L-type; adrenergic; hippocampus; imaging

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Received May 3, 2004; revised August 13, 2004; accepted August 13, 2004.

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