Calcium-dependent gating of Voltage-gated ion channels

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Calcium Dependent Inactivation: 
A Ca²⁺-regulated feedback mechanism

	Ca2+ entering through channel
	Requires no cytoplasmic components
		Ca2+ sensor is near channel pore
	Develops rapidly

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Conditional Open Probability Analysis (COPA)

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Does Ca²⁺ bind directly to the a_1C subunit?

Does Ca²⁺ bind directly to the a_1C subunit?

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Calcium Dependent Inactivation
of L-type Ca²⁺ Channels

	Calmodulin is the Ca2+ sensor
	CaM is pre-associated with a1C
	The IQ motif is the effector domain in a1C
	The EF-hand is a structural, non Ca2+-sensing domain

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Calcium Dependent Gating
of P/Q Ca²⁺ Channels

	Kinetics of inactivation and facilitation differ from L-type channel gating
	Calmodulin appears to be the Ca2+ sensor and the IQ motif is one effector domain in a1A
	CBD may be another effector domain
	The Ca2+-binding protein CaBP1 regulates inactivation in a Ca2+-independent manner

Ca²⁺-dependent gating of SK channels

Ca²⁺-dependent gating of SK channels

CaM is the Ca²⁺ sensor

CaM is the Ca²⁺ sensor

Gating Switch

Ca²⁺/CaM modulation of
CNG channels

Mechanism of Action

Other channels

	NMDA subtype of excitatory glutamate receptors
	BKCa channels