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Intracellular Ca
2+
([Ca
2+
]
i
) can rise primarily via release from intracellular storage sites (e.g., the endoplasmic reticulum) or via entry across the membrane down the steep concentration gradient (
1
–
3
). Ca
2+
can enter through two main classes of plasma membrane-located Ca
2+
channels: receptor operated and voltage sensitive (
4
–
7
). Voltage-sensitive Ca
2+
channels are involved in a wide and diverse array of physiological responses including neurotransmitter release (
8
). In addition, many guanine nucleotide protein (G) coupled receptors couple to voltage-sensitive Ca
2+
channels to reduce Ca
2+
influx (
9
,
10
).