Different Types of Calcium Channels (original) (raw)

Calcium Channels – An Overview

Encyclopedia of Neuroscience, 2009

Definition ▶Voltage-gated Ca 2± channels are integral membrane proteins forming aqueous pores which open in response to cell depolarization. Ca 2+ channels play a key role in controlling vital functions: they shape the ▶action potential and membrane electrical oscillations and act as gate-controller of Ca 2+ , the most ubiquitous ▶second messenger [1]. As such, Ca 2+ channels are implicated in cardiac, skeletal and smooth ▶muscle contraction (▶excitation-contraction coupling), ▶hormone and neurotransmitter release (▶excitation-secretion coupling) and Ca 2+-dependent processes that modulate short-and long-term cell activity and gene expression (▶excitationtranscription coupling) [2-5]. Characteristics Ca 2+ channels have been grouped into two main classes, based on their threshold of activation: the ▶high voltage-activated (HVA) channels and the ▶low voltageactivated (LVA) channels [4]; although this classification could not be strictly applied since some of the HVA channels activate at significantly low voltages [2]. LVA channels activate " ▶transiently" during small depolarizations near ▶resting membrane potentials (→ ▶Membrane potentialbasics) and are therefore commonly indicated as T-type channels. T-type channels are responsible for ▶low-threshold spikes, oscillatory cell activity, muscle contraction, hormone release, cell growth, differentiation and proliferation [5]. The HVA channels require larger membrane depolarizations to open and are further subdivided into four types (▶L-, N-, P/Q-and R-type Ca 2± channels) based on their structural, pharmacological and biophysical characteristics [2,3]. They are responsible for the sustained depolarizing phase of action potentials, muscle contraction, hormone and neurotransmitter release, gene expression and cell differentiation.

Calcium channels: Structure, function, and classification

Drug Development Research, 1994

Voltage-gated Ca2 ' channels have been exten5ively characterized in terms of their electrophysiological and pharmacological properties [McDonald et al. (1994). Physiol Rev 74. 365-507; Spedding and Paoletti (1992): Pharmacol Kev44:363-376; Tsien and Tsien (1990): Annu Rev Cell Biol 6:715-7601. These studies indicate that there are numerous types of Ca2+ channels, termed L, N, PIQ, R, and T [Zhang et al. (1993): Neuropharmacology 32:1075-10881. Biochemical and molecular biological studies have established that CaL+ channels are multi-subunit complexes composed of an ion-conducting subunit, al (see Fig. I ) , and smaller accessory subunits (a2, p, and sometimes y and a 95 kDa protein). To date (May, 19941, genes for six a , , four p, one u2, and one y have been cloned. Expression studies with cloned a1 have demonstrated that this whunit can determine the voltage and pharmacological sensitivity of the channel. This should allow us to classify the cloned a15 in terms of their type. Unfortunately life i s not that simple. We will review how the accessory subunits are capable of modifying the pharmacological and biophysical characteristics of the channel. Despite these complications, 5 of the 6 a , s can be clawfied as follows: (1) three (, and a q U ) belong to the L-type (dihydropyridine-sensitive), (2) ale is an N-type (w-conotoxin-GVIAsensitive), and (3) a,A is a P (w-aga-IVA-sensitive, also called Q [see : Neuropharmacology 32:1075-10881, herein referred to as PiQ). The sixth a,, aIE, does not display any distinctive pharmacology, thus it has been called an R-type (resistant) The molecular biology of Ca2+ channels has its origins in the biochemical characterization of the skeletal muscle dihydropyridine receptor. This receptorichannel complex was purified, sequenced, cloned, and expressed. Cloning of these cDNAs provided the probes to discover the molecular diversity of Ca2' channels. We will review the cloning, tissue distribution, and functional expression of a1 subunits following a historical path, then review the accessory subunits. o 19% Wdey LISS, Inc

Different types of Ca2+ channels in mammalian skeletal muscle cells in culture

Proceedings of the National Academy of Sciences, 1986

This paper describes the existence of two pharmacologically distinct types of Ca2+ channels in rat skeletal muscle cells (myoballs) in culture. The first class of Ca2+ channels is insensitive to the dihydropyridine (DHP) (+)-PN 200-110; the second class of Ca2+ channels is blocked by low concentrations of (+)-PN 200-110. The two pharmacologically different Ca2+ channels are also different in their voltage and time dependence. The threshold for activation of the DHP-insensitive Ca2+ channel is near -65 mV, whereas the threshold for activation of the DHP-sensitive Ca2+ channel is near -30 mV. Current flowing through the DHP-insensitive Ca2+ channel is transient with relatively fast kinetics. Halfmaximal inactivation for the DHP-insensitive Ca2+ channel is observed at a holding potential Vho.5 = -78 mV and the channel is completely inactivated at -60 mV. Two different behaviors have been found for DHP-sensitive channels with two different kinetics of inactivation (one being about 16 times faster than the other at -2 mV) and two different voltage dependencies. These two different behaviors are often observed in the same myoball and may correspond to two different subtypes of DHP-sensitive Ca'+ channels or to two different modes of expression of one single Ca2+ channel protein.

Different types of calcium channels and secretion from bovine chromaffin cells

European Journal of Neuroscience, 1999

Bovine chromaf®n cells possess several types of Ca 2+ channels, and in¯ux of Ca 2+ is known to trigger secretion. However, discrepant information about the relative importance of the individual subtypes in secretion has been reported. We used whole-cell patch-clamp measurements in isolated cells in culture combined with fura-2 micro¯uorimetry and pharmacological manipulation to determine the dependence of secretion on different types of Ca 2+ channels. We stimulated cells with relatively long depolarizing voltage-clamp pulses in a medium containing 60 mM CaCl 2. We found that, within a certain range of pulse parameters, secretion as measured by membrane capacitance changes was mainly determined by the total cumulative charge of Ca 2+ in¯ow and the basal [Ca 2+ ] level preceding a stimulus. Blocking or reducing the contribution of speci®c types of Ca 2+ channels using either 20 mM nifedipine plus 10 mM nimodipine or 1 mM wCTxGVIA (omega-conotoxin GVIA) or 2 mM wCTxMVIIC (omega-conotoxin MVIIC) reduced secretion in proportion to Ca 2+ charge, irrespective of the toxin used. We conclude that for long-duration stimuli, which release a large fraction of the readily releasable pool of vesicles, it is not so important through which type of channels Ca 2+ enters the cell. Release is determined by the total amount of Ca 2+ entering and by the ®lling state of the readily releasable pool, which depends on basal [Ca 2+ ] before the stimulus. This result does not preclude that other stimulation patterns may lead to responses in which subtype speci®city of Ca 2+ channels matters.

Membrane ion channels as physiological targets for local Ca2+ signalling

Journal of Microscopy, 1999

Ionized calcium plays a central role as a second messenger in a number of physiologically important processes determining smooth muscle function. To regulate a wide range of cellular activities the mechanisms of subcellular calcium signalling should be very diverse. Recent progress in development of visible light-excitable¯uorescent dyes with high af®nity for Ca 2 (such as oregon green 488 BAPTA indicators,¯uo-3 and fura red) and confocal laser scanning microscopy provides an opportunity for direct visualization of subcellular Ca 2 signalling and reveals that many cell function are regulated by the microenvironment within small regions of the cytoplasm (`local control' concept). Here confocal imaging is used to measure and locate changes in [Ca 2 ] i on a subcellular level in response to receptor stimulation in visceral myocytes. We show that stimulation of muscarinic receptors in ileal myocytes with carbachol leading to activation of inositol 1,4,5-trisphosphate receptors (IP 3 Rs) accelerates the frequency of spontaneous calcium sparks (discharged via ryanodine receptors, RyRs) and gives rise to periodic propagating Ca 2 waves oscillating with a frequency similar to that of carbacholactivated cationic current oscillations. Furthermore, by combining the whole-cell patch clamp technique with simultaneous confocal imaging of [Ca 2 ] i in voltage-clamped vascular myocytes we demonstrate that calcium sparks may lead to the opening of either Ca 2-activated Cl À channels or Ca 2-activated K channels, and the discharge of a spontaneous transient inward current (STIC) or a spontaneous transient outward current (STOC), respectively.

The Voltage-Gated Ca 2+ Channel Is the Ca 2+ Sensor Protein of Secretion †

Biochemistry, 2008

Neurotransmitter release involves two consecutive Ca 2+-dependent steps, an initial Ca 2+ binding to the selectivity filter of voltage-gated Ca 2+ channels (VGCC) followed by Ca 2+ binding to synaptic vesicle protein. The unique Ca 2+-binding site of the VGCC is located within the R 1 subunit of the Ca 2+ channel. The structure of the selectivity filter allows for the binding of Ca 2+ , Sr 2+ , Ba 2+ , and La 3+. Despite its cell impermeability, La 3+ supports secretion, which is in contradistinction to the commonly accepted mechanism in which elevation of cytosolic ion concentrations ([Ca 2+ ] i) and binding to synaptotagmin(s) trigger release. Here we show that a Cav1.2-mutated R 1 1.2/L775P subunit which does not conduct Ca 2+ currents supports depolarization-evoked release by means of Ca 2+ binding to the pore. Bovine chromaffin cells, which secrete catecholamine almost exclusively via nifedipine-sensitive Cav1.2, were infected with the Semliki Forest Virus, pSFV R 1 1.2/L775P. This construct also harbored a second mutation that rendered the channel insensitive to nifedipine. Depolarization of cells infected with R 1 1.2/L775P triggered release in the presence of nifedipine. Thus, the initial Ca 2+ binding at the pore of the channel appeared to be sufficient to trigger secretion, indicating that the VGCC could be the primary Ca 2+ sensor protein. The 25% lower efficiency, however, implied that additional ancillary effects of elevated [Ca 2+ ] i were essential for optimizing the overall release process. Our findings suggest that the rearrangement of Ca 2+ ions within the pore of the channel during membrane depolarization triggers secretion prior to Ca 2+ entry. This allows for a tight temporal coupling between the depolarization event and exocytosis of vesicles tethered to the channel. † Supported by the Betty Feffer Foundation (D.A.

Molecular biology of calcium channels

Kidney International, 1995

Pharmacological and electrophysiological studies have established that there are multiple types of voltage-gated Ca2+ channels. Molecular biology has uncovered an even greater number of channel molecules. Thus, the molecular diversity of Ca2+ channels has its basis in the expression of many alpha 1 and beta genes, and also in the splice variants produced from these genes. This ability to mix and match subunits provides the cell with yet another mechanism to control the influx of calcium. Future studies will describe new subunits, the subunit composition of each type of channel, and the cloning of new Ca2+ channel types.