METABOTROPIC GLUTAMATE-RECEPTOR INHIBITION OF VISCERAL AFFERENT POTASSIUM CURRENTS

The effects of metabotropic glutamate receptor activation (mGluR) on v oltage-gated potassium currents have been characterized in visceral se nsory afferent neurons. L-Glutamate is known to be a primary neurotran smitter in visceral afferents which terminate at the level of the nucl eus of the solitary tract (NTS). Synaptic communication between these afferents and the NTS has been shown to involve both postsynaptic iono tropic and presynaptic metabotropic glutamate receptor activation. The purpose of the present study was to determine the effects of mGluR ac tivation on voltage-gated potassium currents in visceral sensory neuro ns. Application of mGluR agonist t-ACPD inhibited both the peak and th e steady state voltage-gated potassium current in 39 out of 56 viscera l afferent neurons tested (70%) by 22.0 +/- 3 and 22.8 +/- 2%, respect ively. Voltage and pharmacological protocols were utilized to isolate the potassium current affected by mGluR activation. Increasing the hol ding potential from - 100 mV to - 30 mV only partially attenuated the inhibitory effects of t-ACPD (decreased effect by 11%), suggesting tha t t-ACPD modulates both a voltage insensitive and a voltage-sensitive potassium current. In addition, 4-aminopyridine (5 mu M) was applied t o eliminate the 4-AP sensitive transient current. Also, this protocol only partially attenuated the inhibitory effects of t-ACPD (decreased effect by 6.3%), suggesting that mGluR activation inhibits both a CAP- sensitive and 4-AP-insensitive potassium current in visceral afferent neurons. Results from this study suggest that mGluRs may regulate visc eral sensory afferent neuronal activity through inhibition of voltage- gated potassium channels.