Effects of divalent cations on muscarinic receptor cationic current in smooth muscle from XXXX small intestine.

@entity3007 @entity1025 @entity840 @entity141 @entity5402
1. Effects of @entity1025 and @entity141 on muscarinic receptor cationic current (Icat) in @entity840 ileal smooth muscle cells have been studied using patch-clamp techniques (whole-cell recording). Icat was activated either by externally applied @entity5402 or, to bypass receptors, by intracellular @entity3007 -gamma-S. 2. Independently of the main permeant cation the current-voltage (I-V) relation for Icat was U-shaped between the reversal potential (usually 0 mV) and very negative potentials such as -120 mV where current could be virtually lost. Adding @entity141 to @entity141 - and @entity1025 -free external solution reduced inward current and made it less U-shaped whereas adding @entity1025 reduced inward current and shifted more positively the potential at which maximum inward current occurred. 3. Activation of the conductance underlying Icat could be described by the Boltzmann relation which was shifted positively by adding @entity141 or @entity1025 . Extracellular @entity141 also distorted the relation by increasing the slope factor; maximal conductance was reduced in all cases. Icat relaxation at negative potentials was accelerated by increasing @entity1025 and slowed down by @entity141 . 4. These data suggest the presence of fixed negative surface charges on or near the muscarinic receptor cationic channel, which allow its modulation through alteration of surface potential. Additional more direct ion binding to and blocking of the channel cannot be ruled out. Some additional effects of @entity141 (if compared with @entity1025 ) could be explained on the assumption that the @entity141 -binding activation site known to be present on the internal side of the channel can be accessible to @entity141 entering through the open channel during muscarinic receptor stimulation, as @entity141 ions contribute to a limited extent to Icat. 5. We conclude that voltage-dependent gating of muscarinic receptor cationic channels is an intrinsic channel property and that @entity141 and @entity1025 have strong modulatory effects.
