Deletion of TRPC4 and TRPC6 in mice impairs smooth muscle contraction and intestinal motility in vivo.

Background & Aims: Downstream effects of muscarinic receptor stimulation in intestinal smooth muscle include contraction and intestinal transit. We thought to determine whether classic transient receptor potential (TRPC) channels integrate the intracellular signaling cascades evoked by the stimulated receptors and thereby contribute to the control of the membrane potential, Ca-influx, and cell responses.

Methods: We created trpc4-, trpc6-, and trpc4/trpc6-gene-deficient mice and analyzed them for intestinal smooth muscle function in vitro and in vivo.

Effects of polyamines on the muscarinic receptor-operated cation current in guinea-pig ileal smooth muscle myocytes.

The effects of extracellular and intracellular polyamines (PAs), spermine and putrescine, on the cation current (mI(CAT)) evoked either by activating muscarinic receptors with carbachol or by intracellularly applied GTPgammaS (in the absence of carbachol) were studied using patch-clamp recording techniques in single guinea-pig ileal myocytes. Extracellular spermine and putrescine rapidly and reversibly inhibited mI(CAT) in a concentration- and voltage-dependent manner with the IC(50) values at -40 mV of about 1 and 5 mM, respectively. Membrane depolarization relieved the blocking action of PAs although cation conductance activation curve remained N-shaped.