N- and P/Q-type Ca²⁺ channels in adrenal chromaffin cells

Ca²⁺ is the most ubiquitous second messenger found in all cells. Alterations in [Ca²⁺]_i contribute to a wide variety of cellular responses including neurotransmitter release, muscle contraction, synaptogenesis and gene expression. Voltage-dependent Ca²⁺ channels, found in all excitable cells (Hille 1992), mediate the entry of Ca²⁺ into cells following depolarization. Ca²⁺ channels are composed of a large pore-forming subunit, called the α₁ subunit, and several accessory subunits. Ten different α₁ subunit genes have been identified and classified into three families, Ca_v1-3 (Dunlap et al. 1995, Catterall 2000). Each α₁ gene produces a unique Ca ²⁺ channel. Although chromaffin cells express several different types of Ca²⁺ channels, this review will focus on the Cav_2.1 and Cav_2.2 channels, also known as P/Q- and N-type respectively (Nowycky et al. 1985, Llinas et al. 1989b, Wheeler et al. 1994). These channels exhibit physiological and pharmacological properties similar to their neuronal counterparts. N-, P/Q and to a lesser extent R-type Ca²⁺ channels are known to regulate neurotransmitter release (Hirning et al. 1988, Horne & Kemp 1991, Uchitel et al. 1992, Luebke et al. 1993, Takahashi & Momiyama 1993, Turner et al. 1993, Regehr & Mintz 1994, Wheeler et al. 1994, Wu & Saggau 1994, Waterman 1996, Wright & Angus 1996, Reid et al. 1997). N- and P/Q-type Ca²⁺ channels are abundant in nerve terminals where they colocalize with synaptic vesicles. Similarly, these channels play a role in neurotransmitter release in chromaffin cells (Garcia et al. 2006). N- and P/Q-type channels are subject to many forms of regulation (Ikeda & Dunlap 1999). This review pays particular attention to the regulation of N- and P/Q-type channels by heterotrimeric G-proteins, interaction with SNARE proteins, and channel inactivation in the context of stimulus-secretion coupling in adrenal chromaffin cells.