Voltage-dependent calcium channels in rat midbrain dopamine neurons: modulation by dopamine and GABAB receptors

Abstract

1. Voltage-dependent calcium channels were studied with whole cell voltage-clamp recordings from neurons enzymatically dispersed from the ventral mesencephalon of rat brains (postnatal days 3-10) and identified as dopamine neurons by 5,7-dihydroxytryptamine autofluorescence. 2. Dopamine neurons had large high-threshold calcium currents activated by depolarizations positive to -50 mV. Different components of calcium channel current were not readily distinguishable by voltage dependence or kinetics, but pharmacological experiments showed the existence of different channel types. The overall current had significant components blocked by nimodipine (28%), by omega-conotoxin GVIA (22%), and by omega-agatoxin-IVA (omega-Aga-IVA) (37%), and there was a significant amount of current (16%) remaining in saturating concentrations of all three blockers. 3. High-threshold calcium current was reversibly reduced by the gamma-aminobutyric acid-B (GABAB) receptor agonist baclofen and by dopamine and the D2 receptor agonist quinpirole. Inhibition by GABAB or dopamine agonists developed and reversed within seconds. 4. Quinpirole reduced both omega-conotoxin-sensitive and omega-Aga-IVA-sensitive components of calcium current. 5. With physiological ionic conditions, inward calcium currents were outweighed by outward currents, in part through calcium-activated potassium channels activated by omega-conotoxin-sensitive and omega-Aga-IVA-sensitive calcium entry.

Resurgent Sodium Current and Action Potential Formation in Dissociated Cerebellar Purkinje Neurons

“…In particular, the large P-type calcium currents present in Purkinje neurons would be active at these voltages of Ϫ50 to Ϫ30 mV and would be inactivated only partially (Regan, 1991). Calcium entry through calcium channels, however, may well activate counterbalancing potassium currents through calcium-activated potassium channels (Cardozo and Bean, 1995). Whatever other ionic currents flow between the first and spikes of the action potential, the sodium current flowing during this time is a substantial part of the net current, as obtained from ϪC m dV/dt.…”

IhChannels Contribute to the Different Functional Properties of Identified Dopaminergic Subpopulations in the Midbrain

“…In addition, we have recently shown by quantitative single-cell real-time PCR that differences in transcript numbers for Kv4␣ and Kv4␤ subunits control the A-type potassium channel density and pacemaker frequency in DA SN neurons (Liss et al, 2001). Other obvious candidates that might contribute to functional diversity are persistent sodium channels (Grace, 1991;Catterall, 2000;Maurice et al, 2001) and low-threshold calcium channels (Kang and Kitai, 1993;Cardozo and Bean, 1995;Perez-Reyes, 1999).…”

Electrophysiological Pharmacology of Mesencephalic Dopaminergic Neurons

“…The slow after-hyperpolarization is very sensitive to apamin, and plays a significant role in regulating the firing pattern of dopaminergic neurons Ping and Shepard 1996). A number of pharmacologically and electrophysiologically distinct low-and high-threshold calcium conductances have been identified in midbrain dopaminergic neurons (e.g., Llinás et al 1984;Nedergaard et al 1988Nedergaard et al , 1993Nedergaard and Greenfield 1992;Kang and Kitai 1993a,b;Cardozo and Bean 1995;Galarraga and Bargas 1995;Wilson and Callaway 2000). Dopaminergic neurons also exhibit several different types of voltage-dependent potassium channels (Silva et al 1990).…”

“…Dopaminergic neurons also exhibit several different types of voltage-dependent potassium channels (Silva et al 1990). A transient, 4-aminopyridine (4-AP)-sensitive, TEA-insensitive A-current that is largely inactivated at the most stable subthreshold membrane potentials is expressed, as is a sustained outward current and at least two different types of calciumactivated potassium current (Silva et al 1990;Cardozo and Bean 1995), plus the inwardly rectifying I h mentioned above. Although the conductances responsible for the bursty and random firing patterns have not yet been identified conclusively, it appears that the pacemaker firing pattern emerges as a result of an intrinsic membrane potential oscillation, resulting from a low threshold, non-inactivating calcium conductance, and a calcium-activated potassium conductance (Harris et al 1989;Yung et al 1991;Nedergaard and Greenfield 1992;Kang and Kitai 1993a,b;Wilson and Callaway 2000).…”

“…However, as described above, subsequent electrophysiological studies revealed that the prolonged spike afterhyperpolarization and long interspike intervals were due largely to a calcium activated potassium conductance (Kita et al 1986;Shepard and Bunney 1988;Ping and Shepard 1996), and not to dopamine. Interestingly enough, autoreceptor stimulation in dissociated dopaminergic neurons has been shown to reduce calcium entry through w-conotoxin and w-AgaIVA-sensitive calcium channels which leads to a reduction in the calcium-activated potassium current (Cardozo and Bean 1995).…”