Facilitation of L-type Ca2+ channels in dendritic spines by activation of beta2 adrenergic receptors.

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 beta2 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 microm) significantly reduced Ca2+ transients in both spines and their parent dendrites (approximately 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 microm) reduced spine Ca2+ transients by approximately 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 microm) significantly enhanced the spine Ca2+ transients by 40-50%. Activation of beta2 adrenergic receptors with salbutamol (40 microm) or formoterol (5 microm) 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 microm) or when cAMP-dependent protein kinase A (PKA) was inhibited with KT5720 (3 microm), Rp-cAMPS (Rp-adenosine cyclic 3',5'-phosphorothioate) (100 microm), or PKI (100 microm). 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 beta2 adrenergic receptor through PKA in a highly compartmentalized manner.