Voltage‐ and time‐dependent properties of the recombinant rat vanilloid receptor (rVR1)

摘要: Current rectification is a common property of both ligand- and voltage-gated ion channels (Hille, 1992). There are many good examples the physiological importance process. Specifically with regard to nervous system, early studies highlighted doubly rectifying at electrical synapses in invertebrates, which allow excellent bidirectional communication depolarization but poor transmission hyperpolarization (Baylor & Nicholls, 1969; Acklin, 1988). More recent work has uncovered pivotal role NMDA receptor synaptic integration plasticity (Collingridge Watkins, 1994). Current can occur for any several reasons. In its simplest form, arises from unequal distribution permeant species across lipid bilayer (Goldman, 1943; Hodgkin Katz, 1949). Voltage dependence probability channel opening also source macroscopic current commonly responsible current-voltage properties channels. other instances, voltage-dependent block activity by physical entity produce substantial may even result regions negative slope conductance. Examples this mechanism include Mg2+ (Nowak et al. 1984) polyamine certain inwardly K+ (Lopatin 1994). The observation single-channel currents under simplified recording conditions, e.g. use bi-ionic or symmetrical limits possible sources usually suggests clear voltage permeation pathway 1992). The pungent alkaloid capsaicin long been known outwardly Na+/K+/Ca2+-mediated responses voltage-clamped sensory neurones (Heyman Rang, 1985; Marsh 1987; Wood 1988; Bevan Szolcsanyi, 1990; Oh 1996; Zeilhofer 1997). Recently was cloned rat tissue (Caterina It named vanilloid receptor-1 (VR1) after ability respond range moieties including itself. Heterologous expression (rVR1) revealed that addition capsaicin-mediated activation, it acts as polymodal detector, being capable responding changes pH temperature (Tominaga 1998). Whether activated chemically, H+, heat, mediated recombinant rVR1 exhibit outward 1997; Tominaga 1998), thus resemble elicited heat (Oh Piper 1999; Nagy 1999). Initial indicate these extend level, ruling out number mechanisms their generation 1998; 1999). In study we have characterized capsaicin-, voltage- time-dependent expressed HEK 293 cells. Although our findings concerning basic agree broadly previous reports 1998) results differ they demonstrate time dependent. We shown pronounced not instantaneous – relatively slow develop recover response membrane potential. To knowledge, represent novel finding ligand-gated suggest coincident action potential firing serve facilitate vivo.