Regulation of calcium currents by chemokines and their receptors.

We investigated the modulation of voltage dependent Ca(2+) currents by chemokine receptors in heterologous expression systems and neurons. Fractalkine, SDF-1alpha, RANTES and MDC inhibited the I(Ba) in CX3CR1-, CXCR4-, CCR5- and CCR4-expressing G1A1 cells, respectively. The I(Ba) inhibition was voltage-dependent, exhibited prepulse facilitation, and was blocked by N-ethylmaleimide and pertussis toxin pretreatment, indicating that it was mediated by Gi/Go. Some chemokines also inhibited the I(Ba) in subpopulations of dorsal root ganglion neurons and area postrema/nucleus tractus solitarius neurons. These data provide evidence that chemokines can potentially modulate neuronal signaling through the inhibition of neuronal Ca(2+) currents.