Ch 4. Voltage-gated Ca2+ channel < Role of Ca2+ > Membrane depolarization action potential generation Muscle contraction Secretion: Exocytosis Enzyme activation & Inactivation Channel modulation Gating channel 1952 Fatt, Katz : In some animals, Ca2+ generates Action Potentials Ex1) Sr2+ (strontium) spike (Fig. 4.1) Ex2) ICa in whole cells of Snail neurons and chromafin cells (fig. 4.2) Ica with TTX and TEA

Ca2+ channels shape Action potentials in heart, vascular smooth muscle, and some neurons (Fig 4.4)

IV-curve of Ica Why bell shape? Because of reduction in Driving Force  

Ca2+ transduces electrical signals and cellular responses (Fig. 4.5) Ca2+ also gates channels Ca2+-activated K+ channel ( Maxi-K+ ) Ca2+-activated Cl- channel ( Anoctamine 1) Ca2+-activated cation channel (TRPM4)   Ca2+ activates enzymes: Calcineurin, CAMKII, etc

< Types of voltage-gated Ca2+ channel > by Richard Tsien   T-type L-type N-type Duration transient Long medium Nomenclature CaV 3.1~3.3 CaV 1.1~1.4 CaV 2.1~2.3 Activation Voltage LVA (low voltage activated) HVA (high voltage activated) Conductance Small ( 8pS ) Large ( 25pS ) Medium ( 13pS ) Blocker Ni Dihydropyridine ( nifedipine ) conotoxin GVIA Ba2+ current (IBa) (Equivalent of Ica and K+ ch blocker)

IV curves of LVA, HVA Ca2+ channels Why current becomes smaller after peak? I = i · n · Po n Po : increase i : decrease due to decreasing driving force

Fig. 4-12 T-type & L-type Ca2+ channel Single channel currents

T-type Ca2+ channel: Ca2+-dependent inactivation (Fig. 4-19) Fig. 4. 13 Ca2+ channel antagonists and Agonists Blockers: verapamil, Diltiazam, Dihydropyridine (Nifedipine) Agonist: Bay K 8644 T-type Ca2+ channel: Ca2+-dependent inactivation (Fig. 4-19)

Voltage-gated Calcium channel structure CaVβ is shown in dark blue and interacts with its high-affinity binding site on the I–II intracellular loop known as the “α-interaction domain, AID”. CaM is shown bound to the C-terminal cytoplasmic tail at the site of the IQ domain. The membrane associated CaVα2δ subunit is shown in orange and green