1. Chapter 7 Metabotropic Channels Ligand-gated channel Metabotropic channel Ligand-gated channels nAchR NMDAR, AMPA & KAR GABA A R P 2 X 5-HT 3

2. Metabotropic channels GIRK ATP-sensitive K channel (I k,ATP ) CNG channel(cyclic nucleotide-gated ch.) BK channel (Ca2+ activated K+ channel) ANO1 (Ca2+ activated Cl- channel) Some TRP channels Many others Ion channels are modulated by Second messengers : Calcium, cAMP, cGMP, ADPR, IP3, DAG, HPETE, etc Cofactors Enzymes : kinases

3. GIRK channel Activated by G βγ subunit Parasympathetic nerve stimulation: Acetylcholine → M2R(GPCR) → G βγ → GIRK → Hyperpolarization → Heart rate↓ Cf) Membrane-delimited pathway Single ch currents Cell-attached Inside-out GTP

4. Cyclic-nucleotide gated (CNG) channel Cation Channel with 6 TM Activated by cGMP and cAMP Light → rhodopsin (GPCR) → G transducer → PDE → cGMP↓ → CNG channel closing → Hyperpolarization → Light signals

6. Ca2+ activated channels Ca2+-activated K+ channels (BK, IK or SK channel) Ca2+-activated Cl- channels (Anoctamin 1 & 2: TMEM16A & B)

7. Modulation of Channel Functions by Cellular Signals Sympathetic nerve stimulation NE → β1 receptor → Adenylate cyclase → cAMP↑ → PKA → phosphorylation of L-type VGCC → Augmented activity of VGCC → Ca2+ ↑ → Myocardiac contractility↑ & Heart rate↑