1. 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

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

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

4. 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

5. < 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)

6. 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

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

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

9. 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