Metabotropic glutamate receptor inhibition of visceral afferent potassium currents.
The effects of metabotropic glutamate receptor activation (mGluR) on voltage-gated potassium currents have been characterized in visceral sensory afferent neurons. L-Glutamate is known to be a primary neurotransmitter in visceral afferents which terminate at the level of the nucleus of the solitary tract (NTS). Synaptic communication between these afferents and the NTS has been shown to involve both postsynaptic ionotropic and presynaptic metabotropic glutamate receptor activation. The purpose of the present study was to determine the effects of mGluR activation on voltage-gated potassium currents in visceral sensory neurons. Application of mGluR agonist t-ACPD inhibited both the peak and the steady state voltage-gated potassium current in 39 out of 56 visceral afferent neurons tested (70%) by 22.0 +/- 3 and 22.8 +/- 2%, respectively. Voltage and pharmacological protocols were utilized to isolate the potassium current affected by mGluR activation. Increasing the holding potential from -100 mV to -30 mV only partially attenuated the inhibitory effects of t-ACPD (decreased effect by 11%), suggesting that t-ACPD modulates both a voltage insensitive and a voltage-sensitive potassium current. In addition, 4-aminopyridine (5 microM) was applied to 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 4-AP-sensitive and 4-AP-insensitive potassium current in visceral afferent neurons. Results from this study suggest that mGluRs may regulate visceral sensory afferent neuronal activity through inhibition of voltage-gated potassium channels.
Hay
M
M
Department of Physiology, University of Texas Health Science Center, San Antonio 78284, USA.
Lindsley
K A
KA
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D015640:Ion Channel Gating; D008564:Membrane Potentials / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects*; D026902:Potassium Channel Blockers; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D014781:Viscera / Q000187:drug effects*
D026902:Potassium Channel Blockers; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D015761:4-Aminopyridine