Voltage gated calcium channels in human dorsal root ganglion neurons.

ABSTRACT Voltage gated calcium currents (VGCCs) in sensory neurons underlie processes ranging from neurotransmitter release to gene expression and remain a therapeutic target for the treatment of pain. Yet virtually all we know about VGCCs has been obtained through the study of rodent sensory neurons and heterologously expressed channels. To address this, high voltage activated (HVA) Ca2+ currents in dissociated human and rat dorsal root ganglion (DRG) neurons were characterized with whole cell patch clamp techniques. The HVA currents from both species shared basic biophysical and pharmacological properties. However, HVA currents in human neurons differed from those in the rat in at least three potentially important ways: (1) Ca2+ current density was significantly smaller, (2) the proportion of nifedipine-sensitive currents was far greater, and (3) a subpopulation of human neurons displayed relatively large constitutive current inhibition. These results highlight the need to for the study of native proteins in their native environment prior to initiating costly clinical trials.