E G Anderson | PubMed Health

The effects of changes in external K+, Ca2+, and Mg2+ concentrations on 5-HT2- and 5-HT3 receptor-mediated depolarizations of the resting membrane potential in rat dorsal root ganglion (DRG) cells was studied. In cells exhibiting a 5-HT2-mediated response, 5-HT and alpha-methyl 5-HT depolarized the resting membrane potential (RMP) and increased the slope of the current-voltage (I/V) relationship. The equilibrium potential (Er) for the depolarization was linearly related to the logarithm of the [K+]o, indicating the depolarization resulted from a decrease in resting K+ conductance. In a subpopulation of large-diameter acutely dissociated DRG neurons recorded from using the whole-cell patch-clamp configuration, 5-HT produced an inward shift in the current required to hold cells at -60 mV. This inward shift in holding current was associated with a reduction in membrane conductance and reversed near Ek. This data suggests that the 5-HT2 receptor-mediated depolarization and increase in R(in) seen in intact DRG preparation is produced by blockade of an outward K+ leak current. Increases in [K+]o reduced the increase in R(in) and depolarization induced by 5-HT with 50% inhibition of the depolarization occurring at 8.3 mM of [K+]o. Half-normal Ca2+ (1.2 mM) produced a downward shift of the 5-HT concentration-response curve, reducing the maximal response by 40%, with minimal effect on the half-maximal response. Mg2+ ions did not affect this 5-HT response. In cells exhibiting a 5-HT3 receptor response, 5-HT and 2-methyl-5-HT produced depolarization with decreased R(in). The Er for this depolarizing response (-30.2 +/- 1.8 mV) became less negative (-11.5 mV) in 10 mM [K+]o with minimal effect on the amplitude of the depolarization. In Na(+)-free superfusate, the 5-HT-induced depolarization was converted to hyperpolarization. This indicated the 5-HT3 response increased a mixed Na+/K+ conductance. Elevated Ca2+ or Mg2+ markedly reduced the 5-HT3 response. Incubation with 3.5 mM Ca2+ shifted the 5-HT concentration-response curve downward and to the right, decreasing the maximal response by 49% and increasing the EC50 by 10-fold. Elevated Mg2+ produced similar effects. In cells where both 5-HT2- and 5-HT3-mediated responses could be demonstrated, the elevation of K+ or the reduction of Ca2+ converted a 5-HT2 response to a 5-HT3 response. The above data suggest that elevation of [K+]o or reduction of [Ca2+]o produced by rapid firing rates of sensory neurons will favor the expression of 5-HT3 responses over 5-HT2 responses.

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PubMed1997