Ca Current in Rabbit Carotid Body Glomus Cells Is Conducted by Multiple Types of High-Voltage–Activated Ca Channels

Overholt, Jeffrey L. and Nanduri R. Prabhakar. Ca current leads to a Ca-dependent release of neurotransmitter(s) in rabbit carotid body glomus cells is conducted by multiple types from glomus cells, which activates sensory fibers of the of high-voltage–activated Ca channels. J. Neurophysiol. 78: carotid sinus nerve. Several lines of evidence support the 2467–2474, 1997. Carotid bodies are sensory organs that detect idea that extracellular Ca is involved in transduction of changes in arterial oxygen. Glomus cells are presumed to be the the hypoxic stimulus. Removal of extracellular Ca abolinitial sites for sensory transduction, and Ca-dependent neuroished or attenuated the sensory response to hypoxia (Shiratransmitter release from glomus cells is believed to be an obligatory hata and Fitzgerald 1991) and diminished the hypoxia-instep in this response. Some information exists on the Ca channels duced neurotransmitter release in in vitro preparations in rat glomus cells. However, relatively little is known about the (Obeso et al. 1992) and isolated glomus cells (Montoro et types of Ca channels present in rabbit glomus cells, the species in which most of the neurotransmitter release studies have been al. 1996; Urena et al. 1994). These studies showed that performed. Therefore we tested the effect of specific Ca channel hypoxia evokes a secretory response in glomus cells; extrablockers on current recorded from freshly dissociated, adult rabbit cellular Ca is required for this response and voltage-gated carotid body glomus cells using the whole cell configuration of Ca channels are involved. the patch-clamp technique. Macroscopic Ba current elicited from It is well-known that neuronal cells express multiple types a holding potential of 080 mV activated at a Vm of approximaely of Ca channels in a single cell, which can be involved in 030 mV, peaked between 0 and /10 mV and did not inactivate neurotransmitter release (Dunlap et al. 1995). Traditionally, during 25-ms steps to positive test potentials. Prolonged (É2 min) Ca currents have been categorized as either high(HVA) depolarized holding potentials inactivated the current with a V1/2 or low(LVA) voltage–activated. HVA and LVA currents of 047 mV. There was no evidence for T-type channels. On steps can be distinguished readily using whole cell patch clamp to 0 mV, 6 mM Co decreased peak inward current by 97 { 1% (mean { SE). Nisoldipine (2 mM), 1 mM v-conotoxin GVIA, based on their differing voltage dependencies. There are a and 100 nM v-agatoxin IVa each blocked a portion of the macronumber of distinct channels that underlie HVA currents. scopic Ca current (30 { 5, 33 { 5, and 19 { 3% after rundown However, identifying specific channels underlying HVA correction, respectively) . Simultaneous application of these blockconductance based on their biophysical characteristics can ers revealed a resistant current that was not affected by 1 mM be misleading (Plummer et al. 1989). Generally, channels v-conotoxin MVIIC. This resistant current constituted 27 { 5% underlying HVA conductances are identified pharmacologiof the total macroscopic Ca current. Each blocker had an effect cally when using whole cell patch (e.g., Randall and Tsien in every cell so tested. However, the relative proportion of current 1995). Using specific toxins, HVA channels have been idenblocked varied from cell to cell. These results suggest that L, N, tified as L type, N type, and P/Q type based on their sensitivP, and resistant channel types each conduct a significant proportion ity to dihydropyridines, v-conotoxin GVIA, and v-agatoxin of the macroscopic Ca current in rabbit glomus cells. HypoxiaIVa, respectively. v-Conotoxin MVIIC, a relatively less speinduced neurotransmitter release from glomus cells may involve