Postnatal rat nigrostriatal dopaminergic neurons exhibit five types of potassium conductances

Abstract

1. We have investigated the electrical properties of neurons acutely dissociated from the substantia nigra zona compacta (SNZC) of the postnatal rat with whole cell patch-clamp recordings. Retrogradely labeled nigrostriatal neurons were identified with the use of rhodamine-labeled fluorescent latex microspheres. Over 90% of the rhodamine-labeled neurons in the SNZC demonstrated formaldehyde/glutaraldehyde-induced catecholamine fluorescence, indicating that they were dopaminergic (DA) neurons. 2. DA neurons had 15-20 microns ovoid or fusiform-shaped cell bodies with 2-3 thick proximal processes. Labeled neurons generated spontaneous action-potential activity in both regular and irregular patterns. These cells exhibited input resistances of 300-600 M omega and action-potential amplitudes of 60-80 mV. Locally applied dopamine inhibited the spontaneous activity of these neurons by hyperpolarizing the cells. 3. Outward currents were examined with voltage-clamp recordings using a tetrodotoxin (TTX)-containing medium. In all DA cells, depolarizing voltage commands activated several components of outward current depending on the holding potential of the cell. When cells were held at -40 mV (or more positive), voltage steps activated a sustained outward current. If the membrane potential was held more negative than -50 mV, a rapidly activating and inactivating component of outward current response could also be detected. 4. From a hyperpolarized holding potential (-90 mV) the transient outward current activated with depolarizing commands to -55 mV, peaking within 5 ms. The current inactivated with a monoexponential time constant of 53 +/- 4 (SE) ms. At more positive holding potentials (-40 mV) the steady-state inactivation of the current could be removed by applying a conditioning hyperpolarizing prepulse. In response to a fixed depolarizing voltage step, half-maximal inactivation occurred at about -65 mV. The transient current was blocked by 4-aminopyridine (4-AP). 5. The sustained outward currents were isolated by holding the cells at -40 mV. Two components of sustained outward current were distinguished by their sensitivity to the calcium channel blockers Co2+ (5 mM) and/or Cd2+ (200 microM). The current remaining in the presence of Co2+/Cd2+ was activated by depolarizing voltage commands more positive than -40 mV.(ABSTRACT TRUNCATED AT 400 WORDS)

An Increase in AMPA and a Decrease in SK Conductance Increase Burst Firing by Different Mechanisms in a Model of a Dopamine Neuron In Vivo

“…The restriction of calcium dynamics to the soma in the model in this study is an oversimplification, and it has been suggested that dendritic calcium dynamics drive pacemaking (Chan et al 2005). However, dopamine neurons with only small stumps of dendrites remaining after trituration (Cardozo and Bean 1995) still fire regularly at ϳ3 Hz, as do acutely isolated neurons (Silva et al 1990). The model in this paper, unlike the model of Kuznetsov et al (2006), does not depend on the dendritic calcium entry and activation of the SK current alone to prevent depolarization block at high rates of firing because our model produces increased bursts in the presence of SK blockers, consistent with experimental evidence ( The model presented in this paper is an extension of a previous model (Komendantov et al 2004) that simulated the situation in vivo with constant levels of both glutamatergic and GABAergic input.…”

Electrophysiological Pharmacology of Mesencephalic Dopaminergic Neurons

“…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). 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.…”

“…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).…”

Ethanol Excitation of Dopaminergic Ventral Tegmental Area Neurons Is Blocked by Quinidine

“…These include the BK-type calciumdependent K ϩ current and a delayed rectifier current, which are both blocked by tetraethylammonium (TEA) ion (Silva et al, 1990). In the present study, TEA was used to determine whether block of these two types of K ϩ currents could prevent ethanol excitation of DA VTA neurons.…”

“…Several other types of K ϩ currents have been demonstrated in DA neurons (Silva et al, 1990) that could also contribute to the AHP. These include the BK-type calciumdependent K ϩ current and a delayed rectifier current, which are both blocked by tetraethylammonium (TEA) ion (Silva et al, 1990).…”